Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Konkret geht es um den Diabetes-Patienten mit kardiovaskulären Erkrankungen oder Risiken, die Herzinsuffizienz sowie die kardiovaskuläre Primär- und Sekundärprävention. Sind Sie hier schon auf dem neuesten Stand? Unsere Experten beleuchten, wo und warum das bisherige Procedere geändert werden soll und was in der Praxis sinnvoll ist. Holen Sie sich Ihr Update und 2 CME-Punkte beim MMW-Webinar am 24. April von 17.30 bis 19 Uhr. 
Erweiterte Suche
Anmelden
nach oben
Digestive Diseases and Sciences
Erschienen in: Digestive Diseases and Sciences 4/2022

09.04.2021 | Review

Immune Inhibitory Properties and Therapeutic Prospects of Transforming Growth Factor-Beta and Interleukin 10 in Autoimmune Hepatitis

verfasst von: Albert J. Czaja

Erschienen in: Digestive Diseases and Sciences | Ausgabe 4/2022

Einloggen, um Zugang zu erhalten

Abstract

Transforming growth factor-beta and interleukin 10 have diverse immune inhibitory properties that have restored homeostatic defense mechanisms in experimental models of autoimmune disease. The goals of this review are to describe the actions of each cytokine, review their investigational use in animal models and patients, and indicate their prospects as interventions in autoimmune hepatitis. English abstracts were identified in PubMed by multiple search terms. Full-length articles were selected for review, and secondary and tertiary bibliographies were developed. Transforming growth factor-beta expands the natural and inducible populations of regulatory T cells, limits the proliferation of natural killer cells, suppresses the activation of naïve CD8+ T cells, decreases the production of interferon-gamma, and stimulates fibrotic repair. Interleukin 10 selectively inhibits the CD28 co-stimulatory signal for antigen recognition and impairs antigen-specific activation of uncommitted CD4+ and CD8+ T cells. It also inhibits maturation of dendritic cells, suppresses Th17 cells, supports regulatory T cells, and limits production of diverse pro-inflammatory cytokines. Contradictory immune stimulatory effects have been associated with each cytokine and may relate to the dose and accompanying cytokine milieu. Experimental findings have not translated into successful early clinical trials. The recombinant preparation of each agent in low dosage has been safe in human studies. In conclusion, transforming growth factor-beta and interleukin 10 have powerful immune inhibitory actions of potential therapeutic value in autoimmune hepatitis. The keys to their therapeutic application will be to match their predominant non-redundant function with the pivotal pathogenic mechanism or cytokine deficiency and to avoid contradictory immune stimulatory actions.
Literatur
1.
2.
Czaja AJ. Examining pathogenic concepts of autoimmune hepatitis for cues to future investigations and interventions. World J Gastroenterol 2019;25:6579–6606.PubMedPubMedCentral
3.
Liberal R, Grant CR, Longhi MS, Mieli-Vergani G, Vergani D. Regulatory T cells: mechanisms of suppression and impairment in autoimmune liver disease. IUBMB Life 2015;67:88–97.PubMed
4.
Taubert R, Hardtke-Wolenski M, Noyan F et al. Intrahepatic regulatory T cells in autoimmune hepatitis are associated with treatment response and depleted with current therapies. J Hepatol 2014;61:1106–1114.PubMed
5.
Czaja AJ, Strettell MD, Thomson LJ et al. Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis. Hepatology 1997;25:317–323.PubMed
6.
Czaja AJ. Genetic factors affecting the occurrence, clinical phenotype, and outcome of autoimmune hepatitis. Clin Gastroenterol Hepatol 2008;6:379–388.PubMed
7.
van Gerven NM, de Boer YS, Zwiers A et al. HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in autoimmune hepatitis type-1. Genes Immun 2015;16:247–252.PubMed
8.
Mann DA. Epigenetics in liver disease. Hepatology 2014;60:1418–1425.PubMed
9.
Czaja AJ. Epigenetic changes and their implications in autoimmune hepatitis. Eur J Clin Investig 2018;48:e12899.
10.
Oo YH, Hubscher SG, Adams DH. Autoimmune hepatitis: new paradigms in the pathogenesis, diagnosis, and management. Hepatol Int 2010;4:475–493.PubMedPubMedCentral
11.
12.
Floreani A, Restrepo-Jimenez P, Secchi MF et al. Etiopathogenesis of autoimmune hepatitis. J Autoimmun 2018;95:133–143.PubMed
13.
Trivedi PJ, Adams DH. Mucosal immunity in liver autoimmunity: a comprehensive review. J Autoimmun 2013;46:97–111.PubMed
14.
Mack CL, Adams D, Assis DN et al. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American Association for the Study of Liver Diseases. Hepatology 2020;72:671–722.PubMed
15.
O’Garra A, Arai N. The molecular basis of T helper 1 and T helper 2 cell differentiation. Trends Cell Biol 2000;10:542–550.PubMed
16.
Langrish CL, Chen Y, Blumenschein WM et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005;201:233–240.PubMedPubMedCentral
17.
Chtanova T, Tangye SG, Newton R et al. T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J Immunol 2004;173:68–78.PubMed
18.
Nurieva RI, Chung Y, Hwang D et al. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 2008;29:138–149.PubMedPubMedCentral
19.
Fazilleau N, Mark L, McHeyzer-Williams LJ, McHeyzer-Williams MG. Follicular helper T cells: lineage and location. Immunity 2009;30:324–335.PubMedPubMedCentral
20.
Seo GY, Youn J, Kim PH. IL-21 ensures TGF-beta 1-induced IgA isotype expression in mouse Peyer’s patches. J Leukoc Biol 2009;85:744–750.PubMed
21.
Kelso A. Th1 and Th2 subsets: paradigms lost? Immunol Today 1995;16:374–379.PubMed
22.
Ramadori G, Armbrust T. Cytokines in the liver. Eur J Gastroenterol Hepatol 2001;13:777–784.PubMed
23.
Yu J, Wei M, Becknell B et al. Pro- and antiinflammatory cytokine signaling: reciprocal antagonism regulates interferon-gamma production by human natural killer cells. Immunity 2006;24:575–590.PubMed
24.
Wynn TA. Type 2 cytokines: mechanisms and therapeutic strategies. Nat Rev Immunol 2015;15:271–282.PubMed
25.
Del Prete G, De Carli M, Almerigogna F et al. Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol 1993;150:353–360.PubMed
26.
Akdis CA, Joss A, Akdis M, Faith A, Blaser K. A molecular basis for T cell suppression by IL-10: CD28-associated IL-10 receptor inhibits CD28 tyrosine phosphorylation and phosphatidylinositol 3-kinase binding. FASEB J 2000;14:1666–1668.PubMed
27.
Joss A, Akdis M, Faith A, Blaser K, Akdis CA. IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway. Eur J Immunol 2000;30:1683–1690.PubMed
28.
29.
Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med 1999;190:995–1004.PubMedPubMedCentral
30.
Chen W, Jin W, Hardegen N et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 2003;198:1875–1886.PubMedPubMedCentral
31.
Murai M, Turovskaya O, Kim G et al. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol 2009;10:1178–1184.PubMedPubMedCentral
32.
Ouyang W, Beckett O, Ma Q, Li MO. Transforming growth factor-beta signaling curbs thymic negative selection promoting regulatory T cell development. Immunity 2010;32:642–653.PubMedPubMedCentral
33.
Chaudhry A, Samstein RM, Treuting P et al. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity 2011;34:566–578.PubMedPubMedCentral
34.
Strainic MG, Shevach EM, An F, Lin F, Medof ME. Absence of signaling into CD4(+) cells via C3aR and C5aR enables autoinductive TGF-beta1 signaling and induction of Foxp3(+) regulatory T cells. Nat Immunol 2013;14:162–171.PubMed
35.
Sanjabi S, Oh SA, Li MO. Regulation of the immune response by TGF-beta: from conception to autoimmunity and infection. Cold Spring Harb Perspect Biol 2017;9:a022236.PubMedPubMedCentral
36.
Gleeson D, Heneghan MA. British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis. Gut 2011;60:1611–1629.PubMed
37.
EASL Clinical Practice Guidelines. Autoimmune hepatitis. J Hepatol 2015;63:971–1004.
38.
Czock D, Keller F, Rasche FM, Haussler U. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet 2005;44:61–98.PubMed
39.
Czaja AJ. Drug choices in autoimmune hepatitis: part A—steroids. Expert Rev Gastroenterol Hepatol 2012;6:603–615.PubMed
40.
Fu XQ, Cai JY, Li MJ. Prednisone may rebuild the immunologic homeostasis: alteration of Th17 and Treg cells in the lymphocytes from rats’ spleens after treated with prednisone-containing serum. Mol Genet Genomic Med 2019;7:e00800.PubMedPubMedCentral
41.
Czaja AJ. Promising pharmacological, molecular and cellular treatments of autoimmune hepatitis. Curr Pharm Des 2011;17:3120–3140.PubMed
42.
Liberal R, Krawitt EL, Vierling JM et al. Cutting edge issues in autoimmune hepatitis. J Autoimmun 2016;75:6–19.PubMed
43.
Jones D, Manns MP, Terracciano L, Torbenson M, Vierling JM. Unmet needs and new models for future trials in autoimmune hepatitis. Lancet Gastroenterol Hepatol 2018;3:363–370.PubMed
44.
Czaja AJ. Review article: opportunities to improve and expand thiopurine therapy for autoimmune hepatitis. Aliment Pharmacol Ther 2020;51:1286–1304.PubMed
45.
Vierling JM, Kerkar N, Czaja AJ et al. Immunosuppressive treatment regimens in autoimmune hepatitis: systematic reviews and meta-analyses supporting American Association for the Study of Liver Diseases guidelines. Hepatology 2020;72:753–769.PubMed
46.
47.
Czaja AJ. Factoring the intestinal microbiome into the pathogenesis of autoimmune hepatitis. World J Gastroenterol 2016;22:9257–9278.PubMedPubMedCentral
48.
49.
Czaja AJ. Evolving paradigm for treatment of autoimmune hepatitis. Expert Rev Clin Immunol 2017;13:781–798.PubMed
50.
51.
Halliday N, Dyson JK, Thorburn D, Lohse AW, Heneghan MA. Review article: experimental therapies in autoimmune hepatitis. Aliment Pharmacol Ther 2020;52:1134–1149.PubMed
52.
Lucey DR, Clerici M, Shearer GM. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev 1996;9:532–562.PubMedPubMedCentral
53.
Peters M. Actions of cytokines on the immune response and viral interactions: an overview. Hepatology 1996;23:909–916.PubMed
54.
Akdis M, Aab A, Altunbulakli C et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor beta, and TNF-alpha: receptors, functions, and roles in diseases. J Allergy Clin Immunol 2016;138:984–1010.PubMed
55.
Weiler-Normann C, Schramm C, Quaas A et al. Infliximab as a rescue treatment in difficult-to-treat autoimmune hepatitis. J Hepatol 2013;58:529–534.PubMed
56.
Lim TY, Martinez-Llordella M, Kodela E et al. Low-dose interleukin-2 for refractory autoimmune hepatitis. Hepatology 2018;68:1649–1652.PubMed
57.
Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA. Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol 2006;24:99–146.PubMed
58.
Sanjabi S, Zenewicz LA, Kamanaka M, Flavell RA. Anti-inflammatory and pro-inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity. Curr Opin Pharmacol 2009;9:447–453.PubMedPubMedCentral
59.
Oh SA, Li MO. TGF-beta: guardian of T cell function. J Immunol 2013;191:3973–3979.PubMed
60.
Asadullah K, Sterry W, Volk HD. Interleukin-10 therapy–review of a new approach. Pharmacol Rev 2003;55:241–269.PubMed
61.
62.
Wang X, Wong K, Ouyang W, Rutz S. Targeting IL-10 family cytokines for the treatment of human diseases. Cold Spring Harb Perspect Biol 2019;11:a028548.PubMedPubMedCentral
63.
Neumann C, Scheffold A, Rutz S. Functions and regulation of T cell-derived interleukin-10. Semin Immunol 2019;44:101344.PubMed
64.
Malek TR, Bayer AL. Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol 2004;4:665–674.PubMed
65.
Thornton AM, Donovan EE, Piccirillo CA, Shevach EM. Cutting edge: IL-2 is critically required for the in vitro activation of CD4+CD25+ T cell suppressor function. J Immunol 2004;172:6519–6523.PubMed
66.
Arenas-Ramirez N, Woytschak J, Boyman O. Interleukin-2: biology, design and application. Trends Immunol 2015;36:763–777.PubMed
67.
Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol 2009;27:485–517.PubMed
68.
Zhou L, Lopes JE, Chong MM et al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 2008;453:236–240.PubMedPubMedCentral
69.
Filippi CM, Juedes AE, Oldham JE et al. Transforming growth factor-beta suppresses the activation of CD8+ T-cells when naive but promotes their survival and function once antigen experienced: a two-faced impact on autoimmunity. Diabetes. 2008;7:2684–2692.
70.
Dardalhon V, Awasthi A, Kwon H et al. IL-4 inhibits TGF-beta-induced Foxp3+ T cells and together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells. Nat Immunol 2008;9:1347–1355.PubMedPubMedCentral
71.
Veldhoen M, Uyttenhove C, van Snick J et al. Transforming growth factor-beta “reprograms” the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 2008;9:1341–1346.PubMed
72.
Martinez GJ, Zhang Z, Chung Y et al. Smad3 differentially regulates the induction of regulatory and inflammatory T cell differentiation. J Biol Chem 2009;284:35283–35286.PubMedPubMedCentral
73.
Gagliani N, Amezcua Vesely MC, Iseppon A et al. Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation. Nature 2015;523:221–225.PubMedPubMedCentral
74.
Bettelli E, Carrier Y, Gao W et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006;441:235–238.PubMed
75.
Yang L, Anderson DE, Baecher-Allan C et al. IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 2008;454:350–352.PubMedPubMedCentral
76.
Lin JT, Martin SL, Xia L, Gorham JD. TGF-beta 1 uses distinct mechanisms to inhibit IFN-gamma expression in CD4+ T cells at priming and at recall: differential involvement of Stat4 and T-bet. J Immunol 2005;174:5950–5958.PubMed
77.
Kitani A, Fuss I, Nakamura K et al. Transforming growth factor (TGF)-beta1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGF-beta1-mediated fibrosis. J Exp Med 2003;198:1179–1188.PubMedPubMedCentral
78.
McGeachy MJ, Bak-Jensen KS, Chen Y et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol 2007;8:1390–1397.PubMed
79.
Espevik T, Waage A, Faxvaag A, Shalaby MR. Regulation of interleukin-2 and interleukin-6 production from T-cells: involvement of interleukin-1 beta and transforming growth factor-beta. Cell Immunol 1990;126:47–56.PubMed
80.
Ahuja SS, Paliogianni F, Yamada H, Balow JE, Boumpas DT. Effect of transforming growth factor-beta on early and late activation events in human T cells. J Immunol 1993;150:3109–3118.PubMed
81.
Fargeas C, Wu CY, Nakajima T et al. Differential effect of transforming growth factor beta on the synthesis of Th1- and Th2-like lymphokines by human T lymphocytes. Eur J Immunol 1992;22:2173–2176.PubMed
82.
Heath VL, Murphy EE, Crain C, Tomlinson MG, O’Garra A. TGF-beta1 down-regulates Th2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression. Eur J Immunol 2000;30:2639–2649.PubMed
83.
Letterio JJ, Roberts AB. Regulation of immune responses by TGF-beta. Annu Rev Immunol 1998;16:137–161.PubMed
84.
Roberts AB. Molecular and cell biology of TGF-beta. Miner Electrolyte Metab 1998;24:111–119.PubMed
85.
Govinden R, Bhoola KD. Genealogy, expression, and cellular function of transforming growth factor-beta. Pharmacol Ther 2003;98:257–265.PubMed
86.
Schiller M, Javelaud D, Mauviel A. TGF-beta-induced SMAD signaling and gene regulation: consequences for extracellular matrix remodeling and wound healing. J Dermatol Sci 2004;35:83–92.PubMed
87.
Leask A, Abraham DJ. TGF-beta signaling and the fibrotic response. FASEB J 2004;18:816–827.PubMed
88.
89.
McKaig BC, Hughes K, Tighe PJ, Mahida YR. Differential expression of TGF-beta isoforms by normal and inflammatory bowel disease intestinal myofibroblasts. Am J Physiol Cell Physiol 2002;282:C172-182.PubMed
90.
Ask K, Bonniaud P, Maass K et al. Progressive pulmonary fibrosis is mediated by TGF-beta isoform 1 but not TGF-beta3. Int J Biochem Cell Biol 2008;40:484–495.PubMed
91.
Cowin AJ, Hatzirodos N, Holding CA et al. Effect of healing on the expression of transforming growth factor beta(s) and their receptors in chronic venous leg ulcers. J Investig Dermatol 2001;117:1282–1289.PubMed
92.
Howat WJ, Holgate ST, Lackie PM. TGF-beta isoform release and activation during in vitro bronchial epithelial wound repair. Am J Physiol Lung Cell Mol Physiol 2002;282:L115-123.PubMed
93.
Miyazono K, Ten Dijke P, Ichijo H, Heldin CH. Receptors for transforming growth factor-beta. Adv Immunol 1994;55:181–220.PubMed
94.
Wang J, Zheng H, Sung CC, Richter KK, Hauer-Jensen M. Cellular sources of transforming growth factor-beta isoforms in early and chronic radiation enteropathy. Am J Pathol 1998;153:1531–1540.PubMedPubMedCentral
95.
Yang L, Pang Y, Moses HL. TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol 2010;31:220–227.PubMedPubMedCentral
96.
Todorovic V, Jurukovski V, Chen Y et al. Latent TGF-beta binding proteins. Int J Biochem Cell Biol 2005;37:38–41.PubMed
97.
Marek A, Brodzicki J, Liberek A, Korzon M. TGF-beta (transforming growth factor-beta) in chronic inflammatory conditions—a new diagnostic and prognostic marker? Med Sci Monit 2002;8:RA145–RA151.PubMed
98.
Tran DQ, Andersson J, Wang R et al. GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells. Proc Natl Acad Sci USA 2009;106:13445–13450.PubMedPubMedCentral
99.
Wang R, Zhu J, Dong X et al. GARP regulates the bioavailability and activation of TGFbeta. Mol Biol Cell 2012;23:1129–1139.PubMedPubMedCentral
100.
Lyons RM, Keski-Oja J, Moses HL. Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. J Cell Biol 1988;106:1659–1665.PubMed
101.
Dubois CM, Laprise MH, Blanchette F, Gentry LE, Leduc R. Processing of transforming growth factor beta 1 precursor by human furin convertase. J Biol Chem 1995;270:10618–10624.PubMed
102.
Pesu M, Watford WT, Wei L et al. T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance. Nature 2008;455:246–250.PubMedPubMedCentral
103.
Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFbeta activation. J Cell Sci 2003;116:217–224.PubMed
104.
Jobling MF, Mott JD, Finnegan MT et al. Isoform-specific activation of latent transforming growth factor beta (LTGF-beta) by reactive oxygen species. Radiat Res 2006;166:839–848.PubMed
105.
Murphy-Ullrich JE, Poczatek M. Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology. Cytokine Growth Factor Rev 2000;11:59–69.PubMed
106.
Munger JS, Huang X, Kawakatsu H et al. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 1999;96:319–328.PubMed
107.
Yang Z, Mu Z, Dabovic B et al. Absence of integrin-mediated TGFbeta1 activation in vivo recapitulates the phenotype of TGFbeta1-null mice. J Cell Biol 2007;176:787–793.PubMedPubMedCentral
108.
Travis MA, Reizis B, Melton AC et al. Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. Nature 2007;449:361–365.PubMedPubMedCentral
109.
Lacy-Hulbert A, Smith AM, Tissire H et al. Ulcerative colitis and autoimmunity induced by loss of myeloid alphav integrins. Proc Natl Acad Sci USA 2007;104:15823–15828.PubMedPubMedCentral
110.
Melton AC, Bailey-Bucktrout SL, Travis MA et al. Expression of alphavbeta8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice. J Clin Investig 2010;120:4436–4444.PubMedPubMedCentral
111.
Stockis J, Colau D, Coulie PG, Lucas S. Membrane protein GARP is a receptor for latent TGF-beta on the surface of activated human Treg. Eur J Immunol 2009;39:3315–3322.PubMed
112.
Sun L, Jin H, Li H. GARP: a surface molecule of regulatory T cells that is involved in the regulatory function and TGF-beta releasing. Oncotarget 2016;7:42826–42836.PubMedPubMedCentral
113.
de Jong R, van Lier RA, Ruscetti FW et al. Differential effect of transforming growth factor-beta 1 on the activation of human naive and memory CD4+ T lymphocytes. Int Immunol 1994;6:631–638.PubMed
114.
Massague J, Seoane J, Wotton D. Smad transcription factors. Genes Dev 2005;19:2783–2810.PubMed
115.
Takimoto T, Wakabayashi Y, Sekiya T et al. Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development. J Immunol 2010;185:842–855.PubMed
116.
Gu AD, Wang Y, Lin L, Zhang SS, Wan YY. Requirements of transcription factor Smad-dependent and -independent TGF-beta signaling to control discrete T-cell functions. Proc Natl Acad Sci USA 2012;109:905–910.PubMedPubMedCentral
117.
Kuwahara M, Yamashita M, Shinoda K et al. The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-beta and suppresses T(H)2 differentiation. Nat Immunol 2012;13:778–786.PubMedPubMedCentral
118.
Ebner R, Chen RH, Lawler S, Zioncheck T, Derynck R. Determination of type I receptor specificity by the type II receptors for TGF-beta or activin. Science 1993;262:900–902.PubMed
119.
Attisano L, Carcamo J, Ventura F et al. Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors. Cell 1993;75:671–680.PubMed
120.
Attisano L, Wrana JL, Lopez-Casillas F, Massague J. TGF-beta receptors and actions. Biochim Biophys Acta 1994;1222:71–80.PubMed
121.
Massague J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol 2000;1:169–178.PubMed
122.
Rahimi RA, Leof EB. TGF-beta signaling: a tale of two responses. J Cell Biochem 2007;102:593–608.PubMed
123.
Wrana JL, Attisano L, Wieser R, Ventura F, Massague J. Mechanism of activation of the TGF-beta receptor. Nature 1994;370:341–347.PubMed
124.
Derynck R, Zhang Y, Feng XH. Smads: transcriptional activators of TGF-beta responses. Cell 1998;95:737–740.PubMed
125.
Varga J, Pasche B. Transforming growth factor beta as a therapeutic target in systemic sclerosis. Nat Rev Rheumatol 2009;5:200–206.PubMedPubMedCentral
126.
Chen CH, Seguin-Devaux C, Burke NA et al. Transforming growth factor beta blocks Tec kinase phosphorylation, Ca2+ influx, and NFATc translocation causing inhibition of T cell differentiation. J Exp Med 2003;197:1689–1699.PubMedPubMedCentral
127.
Szabo SJ, Kim ST, Costa GL et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 2000;100:655–669.PubMed
128.
Miller SA, Weinmann AS. Molecular mechanisms by which T-bet regulates T-helper cell commitment. Immunol Rev 2010;238:233–246.PubMedPubMedCentral
129.
Kallies A, Good-Jacobson KL. Transcription factor T-bet orchestrates lineage development and function in the immune system. Trends Immunol 2017;38:287–297.PubMed
130.
Hesslein DG, Lanier LL. Transcriptional control of natural killer cell development and function. Adv Immunol 2011;109:45–85.PubMed
131.
Johnson JL, Rosenthal RL, Knox JJ et al. The transcription factor T-bet resolves memory B cell subsets with distinct tissue distributions and antibody specificities in mice and humans. Immunity 2020;52:842–855.PubMedPubMedCentral
132.
Gorelik L, Constant S, Flavell RA. Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation. J Exp Med. 2002;195:1499–1505.PubMedPubMedCentral
133.
Ho IC, Tai TS, Pai SY. GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation. Nat Rev Immunol 2009;9:125–135.PubMedPubMedCentral
134.
Hosoya T, Maillard I, Engel JD. From the cradle to the grave: activities of GATA-3 throughout T-cell development and differentiation. Immunol Rev 2010;238:110–125.PubMedPubMedCentral
135.
Lentjes MH, Niessen HE, Akiyama Y et al. The emerging role of GATA transcription factors in development and disease. Expert Rev Mol Med 2016;18:e3.PubMedPubMedCentral
136.
Gorelik L, Fields PE, Flavell RA. Cutting edge: TGF-beta inhibits Th type 2 development through inhibition of GATA-3 expression. J Immunol 2000;165:4773–4777.PubMed
137.
Kehrl JH, Roberts AB, Wakefield LM et al. Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes. J Immunol 1986;137:3855–3860.PubMed
138.
Petit-Koskas E, Genot E, Lawrence D, Kolb JP. Inhibition of the proliferative response of human B lymphocytes to B cell growth factor by transforming growth factor-beta. Eur J Immunol 1988;18:111–116.PubMed
139.
Kee BL, Rivera RR, Murre C. Id3 inhibits B lymphocyte progenitor growth and survival in response to TGF-beta. Nat Immunol 2001;2:242–247.PubMed
140.
Bouchard C, Fridman WH, Sautes C. Effect of TGF-beta1 on cell cycle regulatory proteins in LPS-stimulated normal mouse B lymphocytes. J Immunol 1997;159:4155–4164.PubMed
141.
Li MO, Sanjabi S, Flavell RA. Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms. Immunity 2006;25:455–471.PubMed
142.
Travis MA, Sheppard D. TGF-beta activation and function in immunity. Annu Rev Immunol 2014;32:51–82.PubMed
143.
Gorham JD, Lin JT, Sung JL, Rudner LA, French MA. Genetic regulation of autoimmune disease: BALB/c background TGF-beta 1-deficient mice develop necroinflammatory IFN-gamma-dependent hepatitis. J Immunol 2001;166:6413–6422.PubMed
144.
Gorham JD. Transforming growth factor-beta1, Th1 responses, and autoimmune liver disease. Transfusion (Paris) 2005;45:51S-59S.
145.
Shull MM, Ormsby I, Kier AB et al. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 1992;359:693–699.PubMedPubMedCentral
146.
Marie JC, Liggitt D, Rudensky AY. Cellular mechanisms of fatal early-onset autoimmunity in mice with the T cell-specific targeting of transforming growth factor-beta receptor. Immunity 2006;25:441–454.PubMed
147.
Liu Y, Zhang P, Li J et al. A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells. Nat Immunol 2008;9:632–640.PubMed
148.
Zheng Y, Josefowicz S, Chaudhry A et al. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 2010;463:808–812.PubMedPubMedCentral
149.
Schlenner SM, Weigmann B, Ruan Q, Chen Y, von Boehmer H. Smad3 binding to the foxp3 enhancer is dispensable for the development of regulatory T cells with the exception of the gut. J Exp Med 2012;209:1529–1535.PubMedPubMedCentral
150.
Molinero LL, Miller ML, Evaristo C, Alegre ML. High TCR stimuli prevent induced regulatory T cell differentiation in a NF-kappaB-dependent manner. J Immunol 2011;186:4609–4617.PubMed
151.
Wei J, Duramad O, Perng OA et al. Antagonistic nature of T helper 1/2 developmental programs in opposing peripheral induction of Foxp3+ regulatory T cells. Proc Natl Acad Sci USA 2007;104:18169–18174.PubMedPubMedCentral
152.
Geissmann F, Revy P, Regnault A et al. TGF-beta 1 prevents the noncognate maturation of human dendritic Langerhans cells. J Immunol 1999;162:4567–4575.PubMed
153.
Pallotta MT, Orabona C, Volpi C et al. Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells. Nat Immunol 2011;12:870–878.PubMed
154.
Munn DH, Mellor AL. Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol 2013;34:137–143.PubMed
155.
Su HC, Leite-Morris KA, Braun L, Biron CA. A role for transforming growth factor-beta 1 in regulating natural killer cell and T lymphocyte proliferative responses during acute infection with lymphocytic choriomeningitis virus. J Immunol 1991;147:2717–2727.PubMed
156.
Park YP, Choi SC, Kiesler P et al. Complex regulation of human NKG2D-DAP10 cell surface expression: opposing roles of the gammac cytokines and TGF-beta1. Blood 2011;118:3019–3027.PubMedPubMedCentral
157.
Sun C, Fu B, Gao Y et al. TGF-beta1 down-regulation of NKG2D/DAP10 and 2B4/SAP expression on human NK cells contributes to HBV persistence. PLoS Pathog 2012;8:e1002594.PubMedPubMedCentral
158.
Castriconi R, Cantoni C, Della Chiesa M et al. Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proc Natl Acad Sci USA 2003;100:4120–4125.PubMedPubMedCentral
159.
Mills KH. Induction, function and regulation of IL-17-producing T cells. Eur J Immunol 2008;38:2636–2649.PubMed
160.
Esplugues E, Huber S, Gagliani N et al. Control of TH17 cells occurs in the small intestine. Nature 2011;475:514–518.PubMedPubMedCentral
161.
Chalmin F, Mignot G, Bruchard M et al. Stat3 and Gfi-1 transcription factors control Th17 cell immunosuppressive activity via the regulation of ectonucleotidase expression. Immunity 2012;36:362–373.PubMed
162.
Zhao F, Hoechst B, Gamrekelashvili J et al. Human CCR4+ CCR6+ Th17 cells suppress autologous CD8+ T cell responses. J Immunol 2012;188:6055–6062.PubMed
163.
Sharma M, Kaveri SV, Bayry J. Th17 cells, pathogenic or not? TGF-beta3 imposes the embargo. Cell Mol Immunol 2013;10:101–102.PubMedPubMedCentral
164.
Liu HP, Cao AT, Feng T et al. TGF-beta converts Th1 cells into Th17 cells through stimulation of Runx1 expression. Eur J Immunol 2015;45:1010–1018.PubMedPubMedCentral
165.
Wei L, Laurence A, Elias KM, O’Shea JJ. IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. J Biol Chem 2007;282:34605–34610.PubMed
166.
Nurieva R, Yang XO, Martinez G et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 2007;448:480–483.PubMed
167.
Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunol 2010;40:1830–1835.PubMed
168.
Kolls JK, Linden A. Interleukin-17 family members and inflammation. Immunity 2004;21:467–476.PubMed
169.
Fujino S, Andoh A, Bamba S et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut 2003;52:65–70.PubMedPubMedCentral
170.
Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol 2003;171:6173–6177.PubMed
171.
Tzartos JS, Friese MA, Craner MJ et al. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 2008;172:146–155.PubMedPubMedCentral
172.
Wong CK, Ho CY, Li EK, Lam CW. Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus 2000;9:589–593.PubMed
173.
Mangan PR, Harrington LE, O’Quinn DB et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 2006;441:231–234.PubMed
174.
Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 2006;24:179–189.PubMed
175.
Korn T, Bettelli E, Gao W et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 2007;448:484–487.PubMedPubMedCentral
176.
Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 2003;278:1910–1914.PubMed
177.
Zhou L, Ivanov II, Spolski R et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 2007;8:967–974.PubMed
178.
Volpe E, Servant N, Zollinger R et al. A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol 2008;9:650–657.PubMed
179.
McGeachy MJ, Chen Y, Tato CM et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol 2009;10:314–324.PubMedPubMedCentral
180.
Yang XO, Pappu BP, Nurieva R et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 2008;28:29–39.PubMed
181.
Manel N, Unutmaz D, Littman DR. The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol 2008;9:641–649.PubMedPubMedCentral
182.
Ghoreschi K, Laurence A, Yang XP et al. Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature 2010;467:967–971.PubMedPubMedCentral
183.
Komatsu N, Mariotti-Ferrandiz ME, Wang Y et al. Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. Proc Natl Acad Sci USA 2009;106:1903–1908.PubMedPubMedCentral
184.
Komatsu N, Okamoto K, Sawa S et al. Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis. Nat Med 2014;20:62–68.PubMed
185.
Gao GF, Jakobsen BK. Molecular interactions of coreceptor CD8 and MHC class I: the molecular basis for functional coordination with the T-cell receptor. Immunol Today 2000;21:630–636.PubMed
186.
Russell JH, Ley TJ. Lymphocyte-mediated cytotoxicity. Annu Rev Immunol 2002;20:323–370.PubMed
187.
188.
Yu Q, Erman B, Bhandoola A, Sharrow SO, Singer A. In vitro evidence that cytokine receptor signals are required for differentiation of double positive thymocytes into functionally mature CD8+ T cells. J Exp Med 2003;197:475–487.PubMedPubMedCentral
189.
Brugnera E, Bhandoola A, Cibotti R et al. Coreceptor reversal in the thymus: signaled CD4+8+ thymocytes initially terminate CD8 transcription even when differentiating into CD8+ T cells. Immunity 2000;13:59–71.PubMed
190.
Mazzucchelli R, Durum SK. Interleukin-7 receptor expression: intelligent design. Nat Rev Immunol 2007;7:144–154.PubMed
191.
Ouyang W, Oh SA, Ma Q et al. TGF-beta cytokine signaling promotes CD8+ T cell development and low-affinity CD4+ T cell homeostasis by regulation of interleukin-7 receptor alpha expression. Immunity 2013;39:335–346.PubMedPubMedCentral
192.
Thomas DA, Massague J. TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell 2005;8:369–380.PubMed
193.
Pardali K, Moustakas A. Actions of TGF-beta as tumor suppressor and pro-metastatic factor in human cancer. Biochim Biophys Acta 2007;1775:21–62.PubMed
194.
Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 2002;3:349–363.PubMed
195.
Dobaczewski M, Bujak M, Li N et al. Smad3 signaling critically regulates fibroblast phenotype and function in healing myocardial infarction. Circ Res 2010;107:418–428.PubMedPubMedCentral
196.
Verrecchia F, Chu ML, Mauviel A. Identification of novel TGF-beta /Smad gene targets in dermal fibroblasts using a combined cDNA microarray/promoter transactivation approach. J Biol Chem 2001;276:17058–17062.PubMed
197.
Iwano M, Plieth D, Danoff TM et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Investig 2002;110:341–350.PubMedPubMedCentral
198.
Roberts AB, Tian F, Byfield SD et al. Smad3 is key to TGF-beta-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis. Cytokine Growth Factor Rev 2006;17:19–27.PubMed
199.
Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res 2009;19:156–172.PubMed
200.
201.
Krenning G, Zeisberg EM, Kalluri R. The origin of fibroblasts and mechanism of cardiac fibrosis. J Cell Physiol 2010;225:631–637.PubMedPubMedCentral
202.
Piera-Velazquez S, Li Z, Jimenez SA. Role of endothelial-mesenchymal transition (EndoMT) in the pathogenesis of fibrotic disorders. Am J Pathol 2011;179:1074–1080.PubMedPubMedCentral
203.
204.
Dooley S, ten Dijke P. TGF-beta in progression of liver disease. Cell Tissue Res 2012;347:245–256.PubMed
205.
Czaja MJ, Weiner FR, Flanders KC et al. In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis. J Cell Biol 1989;108:2477–2482.PubMed
206.
Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem 2000;275:2247–2250.PubMed
207.
Mauviel A. Transforming growth factor-beta: a key mediator of fibrosis. Methods Mol Med 2005;117:69–80.PubMed
208.
Breitkopf K, Godoy P, Ciuclan L, Singer MV, Dooley S. TGF-beta/Smad signaling in the injured liver. Z Gastroenterol 2006;44:57–66.PubMed
209.
Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev 2008;88:125–172.PubMed
210.
Czaja AJ. Hepatic inflammation and progressive liver fibrosis in chronic liver disease. World J Gastroenterol 2014;20:2515–2532.PubMedPubMedCentral
211.
Seki E, Brenner DA. Recent advancement of molecular mechanisms of liver fibrosis. J Hepatobiliary Pancreat Sci 2015;22:512–518.PubMedPubMedCentral
212.
Seki E, Schwabe RF. Hepatic inflammation and fibrosis: functional links and key pathways. Hepatology 2015;61:1066–1079.PubMed
213.
Nakao A, Afrakhte M, Moren A et al. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature 1997;389:631–635.PubMed
214.
Schnabl B, Kweon YO, Frederick JP et al. The role of Smad3 in mediating mouse hepatic stellate cell activation. Hepatology 2001;34:89–100.PubMed
215.
Furukawa F, Matsuzaki K, Mori S et al. p38 MAPK mediates fibrogenic signal through Smad3 phosphorylation in rat myofibroblasts. Hepatology 2003;38:879–889.PubMed
216.
Del Castillo G, Murillo MM, Alvarez-Barrientos A et al. Autocrine production of TGF-beta confers resistance to apoptosis after an epithelial-mesenchymal transition process in hepatocytes: role of EGF receptor ligands. Exp Cell Res 2006;312:2860–2871.PubMed
217.
Taura K, Miura K, Iwaisako K et al. Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in mice. Hepatology 2010;51:1027–1036.PubMed
218.
Popov Y, Schuppan D. Epithelial-to-mesenchymal transition in liver fibrosis: dead or alive? Gastroenterology 2010;139:722–725.PubMed
219.
Scholten D, Osterreicher CH, Scholten A et al. Genetic labeling does not detect epithelial-to-mesenchymal transition of cholangiocytes in liver fibrosis in mice. Gastroenterology 2010;139:987–998.PubMed
220.
Chu AS, Diaz R, Hui JJ et al. Lineage tracing demonstrates no evidence of cholangiocyte epithelial-to-mesenchymal transition in murine models of hepatic fibrosis. Hepatology 2011;53:1685–1695.PubMed
221.
Pender SL, Breese EJ, Gunther U et al. Suppression of T cell-mediated injury in human gut by interleukin 10: role of matrix metalloproteinases. Gastroenterology 1998;115:573–583.PubMed
222.
Yuan W, Varga J. Transforming growth factor-beta repression of matrix metalloproteinase-1 in dermal fibroblasts involves Smad3. J Biol Chem 2001;276:38502–38510.PubMed
223.
Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology 2008;134:1655–1669.PubMed
224.
Qureshi HY, Sylvester J, El Mabrouk M, Zafarullah M. TGF-beta-induced expression of tissue inhibitor of metalloproteinases-3 gene in chondrocytes is mediated by extracellular signal-regulated kinase pathway and Sp1 transcription factor. J Cell Physiol 2005;203:345–352.PubMed
225.
Qureshi HY, Ricci G, Zafarullah M. Smad signaling pathway is a pivotal component of tissue inhibitor of metalloproteinases-3 regulation by transforming growth factor beta in human chondrocytes. Biochim Biophys Acta 2008;1783:1605–1612.PubMed
226.
Radaeva S, Sun R, Jaruga B et al. Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor necrosis factor-related apoptosis-inducing ligand-dependent manners. Gastroenterology 2006;130:435–452.PubMed
227.
Melhem A, Muhanna N, Bishara A et al. Anti-fibrotic activity of NK cells in experimental liver injury through killing of activated HSC. J Hepatol 2006;45:60–71.PubMed
228.
Jeong WI, Park O, Suh YG et al. Suppression of innate immunity (natural killer cell/interferon-gamma) in the advanced stages of liver fibrosis in mice. Hepatology 2011;53:1342–1351.PubMed
229.
Monteleone G, Kumberova A, Croft NM et al. Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease. J Clin Investig 2001;108:601–609.PubMedPubMedCentral
230.
Boirivant M, Pallone F, Di Giacinto C et al. Inhibition of Smad7 with a specific antisense oligonucleotide facilitates TGF-beta1-mediated suppression of colitis. Gastroenterology 2006;131:1786–1798.PubMed
231.
Monteleone G, Boirivant M, Pallone F, MacDonald TT. TGF-beta1 and Smad7 in the regulation of IBD. Mucosal Immunol 2008;1:S50-53.PubMed
232.
Raz E, Dudler J, Lotz M et al. Modulation of disease activity in murine systemic lupus erythematosus by cytokine gene delivery. Lupus 1995;4:286–292.PubMed
233.
Kuruvilla AP, Shah R, Hochwald GM et al. Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice. Proc Natl Acad Sci USA 1991;88:2918–2921.PubMedPubMedCentral
234.
Thorbecke GJ, Shah R, Leu CH et al. Involvement of endogenous tumor necrosis factor alpha and transforming growth factor beta during induction of collagen type II arthritis in mice. Proc Natl Acad Sci USA 1992;89:7375–7379.PubMedPubMedCentral
235.
King C, Davies J, Mueller R et al. TGF-beta1 alters APC preference, polarizing islet antigen responses toward a Th2 phenotype. Immunity 1998;8:601–613.PubMed
236.
Moritani M, Yoshimoto K, Wong SF et al. Abrogation of autoimmune diabetes in nonobese diabetic mice and protection against effector lymphocytes by transgenic paracrine TGF-beta1. J Clin Investig 1998;102:499–506.PubMedPubMedCentral
237.
Grewal IS, Grewal KD, Wong FS et al. Expression of transgene encoded TGF-beta in islets prevents autoimmune diabetes in NOD mice by a local mechanism. J Autoimmun 2002;19:9–22.PubMed
238.
Racke MK, Dhib-Jalbut S, Cannella B et al. Prevention and treatment of chronic relapsing experimental allergic encephalomyelitis by transforming growth factor-beta 1. J Immunol 1991;146:3012–3017.PubMed
239.
Johns LD, Flanders KC, Ranges GE, Sriram S. Successful treatment of experimental allergic encephalomyelitis with transforming growth factor-beta 1. J Immunol 1991;147:1792–1796.PubMed
240.
Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001;19:683–765.PubMed
241.
Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 2011;29:71–109.PubMed
242.
O’Garra A, Vieira P. T(H)1 cells control themselves by producing interleukin-10. Nat Rev Immunol 2007;7:425–428.PubMed
243.
Xiao S, Brooks CR, Sobel RA, Kuchroo VK. Tim-1 is essential for induction and maintenance of IL-10 in regulatory B cells and their regulation of tissue inflammation. J Immunol 2015;194:1602–1608.PubMed
244.
245.
DiLillo DJ, Matsushita T, Tedder TF. B10 cells and regulatory B cells balance immune responses during inflammation, autoimmunity, and cancer. Ann N Y Acad Sci 2010;1183:38–57.PubMed
246.
Mauri C, Bosma A. Immune regulatory function of B cells. Annu Rev Immunol 2012;30:221–241.PubMed
247.
Bouaziz JD, Le Buanec H, Saussine A, Bensussan A, Bagot M. IL-10 producing regulatory B cells in mice and humans: state of the art. Curr Mol Med 2012;12:519–527.PubMed
248.
249.
Donnelly RP, Dickensheets H, Finbloom DS. The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagocytes. J Interferon Cytokine Res 1999;19:563–573.PubMed
250.
Ho AS, Liu Y, Khan TA et al. A receptor for interleukin 10 is related to interferon receptors. Proc Natl Acad Sci USA 1993;90:11267–11271.PubMedPubMedCentral
251.
Tan JC, Indelicato SR, Narula SK, Zavodny PJ, Chou CC. Characterization of interleukin-10 receptors on human and mouse cells. J Biol Chem 1993;268:21053–21059.PubMed
252.
Pestka S, Krause CD, Sarkar D et al. Interleukin-10 and related cytokines and receptors. Annu Rev Immunol 2004;22:929–979.PubMed
253.
Donnelly RP, Sheikh F, Kotenko SV, Dickensheets H. The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain. J Leukoc Biol 2004;76:314–321.PubMed
254.
Kotenko SV, Gallagher G, Baurin VV et al. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 2003;4:69–77.PubMed
255.
Sheppard P, Kindsvogel W, Xu W et al. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 2003;4:63–68.PubMed
256.
Yoon SI, Jones BC, Logsdon NJ et al. Structure and mechanism of receptor sharing by the IL-10R2 common chain. Structure 2010;18:638–648.PubMedPubMedCentral
257.
Radaeva S, Sun R, Pan HN, Hong F, Gao B. Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology 2004;39:1332–1342.PubMed
258.
Rutz S, Ouyang W. Regulation of interleukin-10 and interleukin-22 expression in T helper cells. Curr Opin Immunol 2011;23:605–612.PubMed
259.
Yang X, Zheng SG. Interleukin-22: a likely target for treatment of autoimmune diseases. Autoimmun Rev 2014;13:615–620.PubMedPubMedCentral
260.
Staples KJ, Smallie T, Williams LM et al. IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3. J Immunol 2007;178:4779–4785.PubMed
261.
262.
Greenfield EA, Nguyen KA, Kuchroo VK. CD28/B7 costimulation: a review. Crit Rev Immunol 1998;18:389–418.PubMed
263.
Dustin ML, Shaw AS. Costimulation: building an immunological synapse. Science 1999;283:649–650.PubMed
264.
Czaja AJ. Understanding the pathogenesis of autoimmune hepatitis. Am J Gastroenterol 2001;96:1224–1231.PubMed
265.
Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol 2005;23:515–548.PubMed
266.
Cai Z, Brunmark AB, Luxembourg AT et al. Probing the activation requirements for naive CD8+ T cells with Drosophila cell transfectants as antigen presenting cells. Immunol Rev 1998;165:249–265.PubMed
267.
Mescher MF, Curtsinger JM, Agarwal P et al. Signals required for programming effector and memory development by CD8+ T cells. Immunol Rev 2006;211:81–92.PubMed
268.
Mescher MF, Agarwal P, Casey KA et al. Molecular basis for checkpoints in the CD8 T cell response: tolerance versus activation. Semin Immunol 2007;19:153–161.PubMedPubMedCentral
269.
Allison JP. CD28-B7 interactions in T-cell activation. Curr Opin Immunol 1994;6:414–419.PubMed
270.
Lenschow DJ, Walunas TL, Bluestone JA. CD28/B7 system of T cell costimulation. Annu Rev Immunol 1996;14:233–258.PubMed
271.
Curtsinger JM, Schmidt CS, Mondino A et al. Inflammatory cytokines provide a third signal for activation of naive CD4+ and CD8+ T cells. J Immunol 1999;162:3256–3262.PubMed
272.
273.
Curtsinger JM, Valenzuela JO, Agarwal P, Lins D, Mescher MF. Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. J Immunol 2005;174:4465–4469.PubMed
274.
de Waal Malefyt R, Haanen J, Spits H et al. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 1991;174:915–924.
275.
de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991;174:1209–1220.
276.
Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature 1992;356:607–609.PubMed
277.
Tan P, Anasetti C, Hansen JA et al. Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. J Exp Med 1993;177:165–173.PubMed
278.
Groux H, Bigler M, de Vries JE, Roncarolo MG. Inhibitory and stimulatory effects of IL-10 on human CD8+ T cells. J Immunol 1998;160:3188–3193.PubMed
279.
Rowbottom AW, Lepper MA, Garland RJ, Cox CV, Corley EG. Interleukin-10-induced CD8 cell proliferation. Immunology 1999;98:80–89.PubMedPubMedCentral
280.
Chikuma S, Bluestone JA. CTLA-4 and tolerance: the biochemical point of view. Immunol Res 2003;28:241–253.PubMed
281.
Chikuma S, Abbas AK, Bluestone JA. B7-independent inhibition of T cells by CTLA-4. J Immunol 2005;175:177–181.PubMed
282.
Chikuma S. CTLA-4, an essential immune-checkpoint for T-cell activation. Curr Top Microbiol Immunol 2017;410:99–126.PubMed
283.
Coomes SM, Kannan Y, Pelly VS et al. CD4(+) Th2 cells are directly regulated by IL-10 during allergic airway inflammation. Mucosal Immunol 2017;10:150–161.PubMed
284.
Walker JA, McKenzie ANJ. TH2 cell development and function. Nat Rev Immunol 2018;18:121–133.PubMed
285.
Huber S, Gagliani N, Esplugues E et al. Th17 cells express interleukin-10 receptor and are controlled by Foxp3(-) and Foxp3+ regulatory CD4+ T cells in an interleukin-10-dependent manner. Immunity 2011;34:554–565.PubMedPubMedCentral
286.
Wang P, Wu P, Siegel MI, Egan RW, Billah MM. Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. J Biol Chem 1995;270:9558–9563.PubMed
287.
Schuetze N, Schoeneberger S, Mueller U et al. IL-12 family members: differential kinetics of their TLR4-mediated induction by Salmonella enteritidis and the impact of IL-10 in bone marrow-derived macrophages. Int Immunol 2005;17:649–659.PubMed
288.
Maloy KJ, Kullberg MC. IL-23 and Th17 cytokines in intestinal homeostasis. Mucosal Immunol 2008;1:339–349.PubMed
289.
Veenbergen S, Li P, Raatgeep HC et al. IL-10 signaling in dendritic cells controls IL-1beta-mediated IFNgamma secretion by human CD4(+) T cells: relevance to inflammatory bowel disease. Mucosal Immunol 2019;12:1201–1211.PubMedPubMedCentral
290.
Cai G, Kastelein RA, Hunter CA. IL-10 enhances NK cell proliferation, cytotoxicity and production of IFN-gamma when combined with IL-18. Eur J Immunol 1999;29:2658–2665.PubMed
291.
Santin AD, Hermonat PL, Ravaggi A et al. Interleukin-10 increases Th1 cytokine production and cytotoxic potential in human papillomavirus-specific CD8(+) cytotoxic T lymphocytes. J Virol 2000;74:4729–4737.PubMedPubMedCentral
292.
Itoh K, Hirohata S. The role of IL-10 in human B cell activation, proliferation, and differentiation. J Immunol 1995;154:4341–4350.PubMed
293.
Levy Y, Brouet JC. Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein. J Clin Investig 1994;93:424–428.PubMedPubMedCentral
294.
Blazar BR, Taylor PA, Smith S, Vallera DA. Interleukin-10 administration decreases survival in murine recipients of major histocompatibility complex disparate donor bone marrow grafts. Blood 1995;85:842–851.PubMed
295.
Lauw FN, Pajkrt D, Hack CE et al. Proinflammatory effects of IL-10 during human endotoxemia. J Immunol 2000;165:2783–2789.PubMed
296.
Calabresi PA, Fields NS, Maloni HW et al. Phase 1 trial of transforming growth factor beta 2 in chronic progressive MS. Neurology 1998;51:289–292.PubMed
297.
Monteleone G, Fantini MC, Onali S et al. Phase I clinical trial of Smad7 knockdown using antisense oligonucleotide in patients with active Crohn’s disease. Mol Ther 2012;20:870–876.PubMedPubMedCentral
298.
Monteleone G, Neurath MF, Ardizzone S et al. Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn’s disease. N Engl J Med 2015;372:1104–1113.PubMed
299.
Marafini I, Monteleone G. Therapeutic oligonucleotides for patients with inflammatory bowel diseases. Biologics 2020;14:47–51.PubMedPubMedCentral
300.
Feagan BG, Sands BE, Rossiter G et al. Effects of Mongersen (GED-0301) on endoscopic and clinical outcomes in patients with active Crohn’s Disease. Gastroenterology 2018;154:61–64.PubMed
301.
Sands BE, Feagan BG, Sandborn WJ et al. Mongersen (GED-0301) for active Crohn’s disease: results of a Phase 3 study. Am J Gastroenterol 2020;115:738–745.PubMed
302.
Denton CP, Merkel PA, Furst DE et al. Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192. Arthritis Rheum 2007;56:323–333.PubMed
303.
Sellon RK, Tonkonogy S, Schultz M et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun 1998;66:5224–5231.PubMedPubMedCentral
304.
Kang SS, Bloom SM, Norian LA et al. An antibiotic-responsive mouse model of fulminant ulcerative colitis. PLoS Med 2008;5:e41.PubMedPubMedCentral
305.
Quattrocchi E, Dallman MJ, Dhillon AP et al. Murine IL-10 gene transfer inhibits established collagen-induced arthritis and reduces adenovirus-mediated inflammatory responses in mouse liver. J Immunol 2001;166:5970–5978.PubMed
306.
Steidler L, Hans W, Schotte L et al. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 2000;289:1352–1355.PubMed
307.
Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 1993;75:263–274.PubMed
308.
Steidler L, Neirynck S, Huyghebaert N et al. Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Nat Biotechnol. 2003;21:785–789.PubMed
309.
Keystone E, Wherry J, Grint P. IL-10 as a therapeutic strategy in the treatment of rheumatoid arthritis. Rheum Dis Clin N Am 1998;24:629–639.
310.
van Roon JA, Lafeber FP, Bijlsma JW. Synergistic activity of interleukin-4 and interleukin-10 in suppression of inflammation and joint destruction in rheumatoid arthritis. Arthritis Rheum 2001;44:3–12.PubMed
311.
van Roon J, Wijngaarden S, Lafeber FP et al. Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation. J Rheumatol 2003;30:648–651.PubMed
312.
van Deventer SJ, Elson CO, Fedorak RN. Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn’s disease. Crohn’s Disease Study Group. Gastroenterology 1997;113:383–389.PubMed
313.
Fedorak RN, Gangl A, Elson CO et al. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn’s disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group. Gastroenterology 2000;119:1473–1482.PubMed
314.
Schreiber S, Fedorak RN, Nielsen OH et al. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn’s disease. Crohn’s Disease IL-10 Cooperative Study Group. Gastroenterology 2000;119:1461–1472.PubMed
315.
Colombel JF, Rutgeerts P, Malchow H et al. Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn’s disease. Gut 2001;49:42–46.PubMedPubMedCentral
316.
Tilg H, van Montfrans C, van den Ende A et al. Treatment of Crohn’s disease with recombinant human interleukin 10 induces the proinflammatory cytokine interferon gamma. Gut 2002;50:191–195.PubMedPubMedCentral
317.
Asadullah K, Sterry W, Stephanek K et al. IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach. J Clin Investig 1998;101:783–794.PubMedPubMedCentral
318.
Asadullah K, Docke WD, Ebeling M et al. Interleukin 10 treatment of psoriasis: clinical results of a phase 2 trial. Arch Dermatol 1999;135:187–192.PubMed
319.
Reich K, Garbe C, Blaschke V et al. Response of psoriasis to interleukin-10 is associated with suppression of cutaneous type 1 inflammation, downregulation of the epidermal interleukin-8/CXCR2 pathway and normalization of keratinocyte maturation. J Investig Dermatol 2001;116:319–329.PubMed
320.
McInnes IB, Illei GG, Danning CL et al. IL-10 improves skin disease and modulates endothelial activation and leukocyte effector function in patients with psoriatic arthritis. J Immunol 2001;167:4075–4082.PubMed
321.
Kimball AB, Kawamura T, Tejura K et al. Clinical and immunologic assessment of patients with psoriasis in a randomized, double-blind, placebo-controlled trial using recombinant human interleukin 10. Arch Dermatol 2002;138:1341–1346.PubMed
322.
Buruiana FE, Sola I, Alonso-Coello P. Recombinant human interleukin 10 for induction of remission in Crohn’s disease. Cochrane Database Syst Rev 2010;11:CD005109.
323.
Demols A, Deviere J. New frontiers in the pharmacological prevention of post-ERCP pancreatitis: the cytokines. JOP 2003;4:49–57.PubMed
324.
Lieb JG 2nd, Draganov PV. Early successes and late failures in the prevention of post endoscopic retrograde cholangiopancreatography. World J Gastroenterol 2007;13:3567–3574.PubMed
325.
Deviere J, Le Moine O, Van Laethem JL et al. Interleukin 10 reduces the incidence of pancreatitis after therapeutic endoscopic retrograde cholangiopancreatography. Gastroenterology 2001;120:498–505.PubMed
326.
Dumot JA, Conwell DL, Zuccaro G Jr et al. A randomized, double blind study of interleukin 10 for the prevention of ERCP-induced pancreatitis. Am J Gastroenterol 2001;96:2098–2102.PubMed
327.
Sherman S, Cheng CL, Costamagna G et al. Efficacy of recombinant human interleukin-10 in prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in subjects with increased risk. Pancreas 2009;38:267–274.PubMed
328.
Van Laethem JL, Marchant A, Delvaux A et al. Interleukin 10 prevents necrosis in murine experimental acute pancreatitis. Gastroenterology 1995;108:1917–1922.PubMed
329.
Chernoff AE, Granowitz EV, Shapiro L et al. A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses. J Immunol 1995;154:5492–5499.PubMed
330.
Fuchs AC, Granowitz EV, Shapiro L et al. Clinical, hematologic, and immunologic effects of interleukin-10 in humans. J Clin Immunol 1996;16:291–303.PubMed
331.
Bayer EM, Herr W, Kanzler S et al. Transforming growth factor-beta1 in autoimmune hepatitis: correlation of liver tissue expression and serum levels with disease activity. J Hepatol 1998;28:803–811.PubMed
332.
Sakaguchi K, Kitano M, Nishimura M et al. Serum level of transforming growth factor-beta1 (TGF-beta1) and the expression of TGF-beta receptor type II in peripheral blood mononuclear cells in patients with autoimmune hepatitis. Hepatogastroenterology 2004;51:1780–1783.PubMed
333.
Gutkowski K, Gutkowska D, Kiszka J et al. Serum interleukin17 levels predict inflammatory activity in patients with autoimmune hepatitis. Pol Arch Intern Med 2018;128:150–156.PubMed
334.
Schramm C, Protschka M, Kohler HH et al. Impairment of TGF-beta signaling in T cells increases susceptibility to experimental autoimmune hepatitis in mice. Am J Physiol Gastrointest Liver Physiol 2003;284:G525-535.PubMed
335.
Paladino N, Flores AC, Fainboim H et al. The most severe forms of type I autoimmune hepatitis are associated with genetically determined levels of TGF-beta1. Clin Immunol 2010;134:305–312.PubMed
336.
Dunning AM, Ellis PD, McBride S et al. A transforming growth factorbeta1 signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer. Cancer Res 2003;63:2610–2615.PubMed
337.
Yokota M, Ichihara S, Lin TL, Nakashima N, Yamada Y. Association of a T29–>C polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to myocardial infarction in Japanese. Circulation 2000;101:2783–2787.PubMed
338.
Bathgate AJ, Pravica V, Perrey C, Hayes PC, Hutchinson IV. Polymorphisms in tumour necrosis factor alpha, interleukin-10 and transforming growth factor beta1 genes and end-stage liver disease. Eur J Gastroenterol Hepatol 2000;12:1329–1333.PubMed
339.
Chaouali M, Fernandes V, Ghazouani E, Pereira L, Kochkar R. Association of STAT4, TGFbeta1, SH2B3 and PTPN22 polymorphisms with autoimmune hepatitis. Exp Mol Pathol 2018;105:279–284.PubMed
340.
Liberal R, Grant CR, Holder BS et al. In autoimmune hepatitis type 1 or the autoimmune hepatitis-sclerosing cholangitis variant defective regulatory T-cell responsiveness to IL-2 results in low IL-10 production and impaired suppression. Hepatology 2015;62:863–875.PubMed
341.
Chen J, Liu W, Zhu W. Foxp3(+) Treg sells are associated with pathological process of autoimmune hepatitis by activating methylation modification in autoimmune hepatitis patients. Med Sci Monit 2019;25:6204–6212.PubMedPubMedCentral
342.
343.
Horan GS, Wood S, Ona V et al. Partial inhibition of integrin alpha(v)beta6 prevents pulmonary fibrosis without exacerbating inflammation. Am J Respir Crit Care Med 2008;177:56–65.PubMed
344.
Puthawala K, Hadjiangelis N, Jacoby SC et al. Inhibition of integrin alpha(v)beta6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis. Am J Respir Crit Care Med 2008;177:82–90.PubMed
345.
Longhi MS, Ma Y, Mitry RR et al. Effect of CD4+ CD25+ regulatory T-cells on CD8 T-cell function in patients with autoimmune hepatitis. J Autoimmun 2005;25:63–71.PubMed
346.
Longhi MS, Ma Y, Bogdanos DP et al. Impairment of CD4(+)CD25(+) regulatory T-cells in autoimmune liver disease. J Hepatol 2004;41:31–37.PubMed
347.
Czaja AJ, Carpenter HA. Progressive fibrosis during corticosteroid therapy of autoimmune hepatitis. Hepatology 2004;39:1631–1638.PubMed
348.
Czaja AJ. Review article: Prevention and reversal of hepatic fibrosis in autoimmune hepatitis. Aliment Pharmacol Ther 2014;39:385–406.PubMed
349.
Mead AL, Wong TT, Cordeiro MF, Anderson IK, Khaw PT. Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery. Investig Ophthalmol Vis Sci 2003;44:3394–3401.
350.
Juarez P, Vilchis-Landeros MM, Ponce-Coria J et al. Soluble betaglycan reduces renal damage progression in db/db mice. Am J Physiol Renal Physiol 2007;292:F321-329.PubMed
351.
Petersen M, Thorikay M, Deckers M et al. Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int 2008;73:705–715.PubMed
352.
Itoh S, ten Dijke P. Negative regulation of TGF-beta receptor/Smad signal transduction. Curr Opin Cell Biol 2007;19:176–184.PubMed
353.
Lan HY. Smad7 as a therapeutic agent for chronic kidney diseases. Front Biosci 2008;13:4984–4992.PubMed
354.
355.
Czaja AJ, Manns MP. Advances in the diagnosis, pathogenesis and management of autoimmune hepatitis. Gastroenterology 2010;139:58–72.PubMed
356.
Burak KW, Swain MG, Santodomino-Garzon T et al. Rituximab for the treatment of patients with autoimmune hepatitis who are refractory or intolerant to standard therapy. Can J Gastroenterol 2013;27:273–280.PubMedPubMedCentral
357.
D’Agostino D, Costaguta A, Alvarez F. Successful treatment of refractory autoimmune hepatitis with rituximab. Pediatrics 2013;132:e526-530.PubMed
358.
Smith KA. Interleukin-2: inception, impact, and implications. Science 1988;240:1169–1176.PubMed
359.
Nelson BH. IL-2, regulatory T cells, and tolerance. J Immunol 2004;172:3983–3988.PubMed
360.
Willems F, Marchant A, Delville JP et al. Interleukin-10 inhibits B7 and intercellular adhesion molecule-1 expression on human monocytes. Eur J Immunol 1994;24:1007–1009.PubMed
361.
Creery WD, Diaz-Mitoma F, Filion L, Kumar A. Differential modulation of B7–1 and B7–2 isoform expression on human monocytes by cytokines which influence the development of T helper cell phenotype. Eur J Immunol 1996;26:1273–1277.PubMed
Metadaten
Titel
Immune Inhibitory Properties and Therapeutic Prospects of Transforming Growth Factor-Beta and Interleukin 10 in Autoimmune Hepatitis
verfasst von
Albert J. Czaja
Publikationsdatum
09.04.2021
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 4/2022
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-021-06968-6

Weitere Artikel der Ausgabe 4/2022

Digestive Diseases and Sciences 4/2022 Zur Ausgabe

FELLOWS AND YOUNG GIS SECTION

Clinical Research Training During Gastroenterology Fellowship

Original Article

Treating the Hardest to Treat: Reframing the Hospital Admission as an Opportunity to Initiate Hepatitis C Treatment

Editorial

Monday, Monday—I Can’t See Clearly Now: How to Improve Bowel Preparation

Correspondence

Risk of Infections with Anti-TNF Agents in Patients with Crohn’s Disease After Elective Surgery

Original Article

Digital Cholangioscopic Interpretation: When North Meets the South

Original Article

Safety and Efficacy of Endoscopic Retrograde Cholangiopancreatography in Nonagenarians: A Systematic Review and Meta-Analysis

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

24.04.2024 | DGIM 2024 | Kongressbericht | Nachrichten

Metformin rückt in den Hintergrund

24.04.2024 | DGIM 2024 | Kongressbericht | Nachrichten

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

24.04.2024 | DGIM 2024 | Kongressbericht | Nachrichten

Thrombophiliescreening – Wenn, dann richtig und nur bei therapeutischer Konsequenz

24.04.2024 | DGIM 2024 | Nachrichten

Bei Senioren mit Prostatakarzinom auf Anämie achten!
weitere anzeigen

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise