nach oben

Seminars in Immunopathology

Erschienen in:

01.01.2016 | Review

Cutaneous immunology: basics and new concepts

verfasst von: Amir S. Yazdi, Martin Röcken, Kamran Ghoreschi

Erschienen in: Seminars in Immunopathology | Ausgabe 1/2016

Einloggen, um Zugang zu erhalten

Abstract

As one of the largest organs, the skin forms a mechanical and immunological barrier to the environment. The skin immune system harbors cells of the innate immune system and cells of the adaptive immune system. Signals of the innate immune system typically initiate skin immune responses, while cells and cytokines of the adaptive immune system perpetuate the inflammation. Skin immune responses ensure effective host defense against pathogens but can also cause inflammatory skin diseases. An extensive crosstalk between the different cell types of the immune system, tissue cells, and pathogens is responsible for the complexity of skin immune reactions. Here we summarize the major cellular and molecular components of the innate and adaptive skin immune system.

Adachi O, Kawai T, Takeda K et al (1998) Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 9:143–150PubMedCrossRef

Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801PubMedCrossRef

Allan RS, Smith CM, Belz GT et al (2003) Epidermal viral immunity induced by CD8alpha + dendritic cells but not by Langerhans cells. Science 301:1925–1928PubMedCrossRef

Asadullah K, Friedrich M, Hanneken S et al (2001) Effects of systemic interleukin-10 therapy on psoriatic skin lesions: histologic, immunohistologic, and molecular biology findings. J Invest Dermatol 116:721–727PubMedCrossRef

Benson JM, Sachs CW, Treacy G et al (2011) Therapeutic targeting of the IL-12/23 pathways: generation and characterization of ustekinumab. Nat Biotechnol 29:615–624PubMedCrossRef

Biedermann T, Kneilling M, Mailhammer R et al (2000) Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2. J Exp Med 192:1441–1452PubMedPubMedCentralCrossRef

Biedermann T, Mailhammer R, Mai A et al (2001) Reversal of established delayed type hypersensitivity reactions following therapy with IL-4 or antigen-specific Th2 cells. Eur J Immunol 31:1582–1591PubMedCrossRef

Biedermann T, Zimmermann S, Himmelrich H et al (2001) IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice. Nat Immunol 2:1054–1060PubMedCrossRef

Bissonnette R, Poulin Y, Guenther L et al (2011) Treatment of palmoplantar psoriasis with infliximab: a randomized, double-blind placebo-controlled study. J Eur Acad Dermatol Venereol 25:1402–1408PubMedCrossRef

10.

Braumuller H, Wieder T, Brenner E et al (2013) T-helper-1-cell cytokines drive cancer into senescence. Nature 494:361–365PubMedCrossRef

11.

Cai Y, Shen X, Ding C et al (2011) Pivotal role of dermal IL-17-producing gamma delta T cells in skin inflammation. Immunity 35:596–610PubMedPubMedCentralCrossRef

12.

Canna SW, De Jesus AA, Gouni S et al (2014) An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nat Genet 46:1140–1146PubMedPubMedCentralCrossRef

13.

Chiu HY, Huang HL, Li CH et al (2015) Increased risk of glomerulonephritis and chronic kidney disease in relation to the severity of psoriasis, concomitant medication, and comorbidity: a nationwide population-based cohort study. Br J Dermatol 173:146–154PubMedCrossRef

14.

Christophers E, Metzler G, Rocken M (2014) Bimodal immune activation in psoriasis. Br J Dermatol 170:59–65PubMedCrossRef

15.

Dombrowski Y, Peric M, Koglin S et al (2011) Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions. Sci Transl Med 3:82ra38PubMedPubMedCentralCrossRef

16.

Drexler SK, Bonsignore L, Masin M et al (2012) Tissue-specific opposing functions of the inflammasome adaptor ASC in the regulation of epithelial skin carcinogenesis. Proc Natl Acad Sci U S A 109:18384–18389PubMedPubMedCentralCrossRef

17.

Duhen T, Geiger R, Jarrossay D et al (2009) Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol 10:857–863PubMedCrossRef

18.

Feldmeyer L, Keller M, Niklaus G et al (2007) The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes. Curr Biol 17:1140–1145PubMedCrossRef

19.

Fink SL, Cookson BT (2006) Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell Microbiol 8:1812–1825PubMedCrossRef

20.

Gagliani N, Vesely MC, Iseppon A et al (2015) Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation. Nature 523:221–225PubMedPubMedCentralCrossRef

21.

Ghoreschi K, Thomas P, Breit S et al (2003) Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease. Nat Med 9:40–46PubMedCrossRef

22.

Ghoreschi K, Laurence A, Yang X et al (2010) Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature 467:967–971PubMedPubMedCentralCrossRef

23.

Ghoreschi K, Laurence A, Yang XP et al (2011) T helper 17 cell heterogeneity and pathogenicity in autoimmune disease. Trends Immunol 32:395–401PubMedPubMedCentralCrossRef

24.

Gomez De Aguero M, Vocanson M, Hacini-Rachinel F et al (2012) Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells. J Clin Invest 122:1700–1711PubMedPubMedCentralCrossRef

25.

Gordon KB, Langley RG, Gottlieb AB et al (2012) A phase III, randomized, controlled trial of the fully human IL-12/23 mAb briakinumab in moderate-to-severe psoriasis. J Invest Dermatol 132:304–314PubMedCrossRef

26.

Grewe M, Gyufko K, Schopf E et al (1994) Lesional expression of interferon-gamma in atopic eczema. Lancet 343:25–26PubMedCrossRef

27.

Griffiths CE, Strober BE, Van De Kerkhof P et al (2010) Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med 362:118–128PubMedCrossRef

28.

Gross O, Yazdi AS, Thomas CJ et al (2012) Inflammasome activators induce interleukin-1alpha secretion via distinct pathways with differential requirement for the protease function of caspase-1. Immunity 36:388–400PubMedCrossRef

29.

Guenova E, Skabytska Y, Hoetzenecker W et al (2015) IL-4 abrogates T(H)17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells. Proc Natl Acad Sci U S A 112:2163–2168PubMedPubMedCentralCrossRef

30.

Harbour SN, Maynard CL, Zindl CL et al (2015) Th17 cells give rise to Th1 cells that are required for the pathogenesis of colitis. Proc Natl Acad Sci U S A 112:7061–7066PubMedPubMedCentralCrossRef

31.

Hauschild A, Weichenthal M, Rass K et al (2010) Efficacy of low-dose interferon {alpha}2a 18 versus 60 months of treatment in patients with primary melanoma of >= 1.5 mm tumor thickness: results of a randomized phase III DeCOG trial. J Clin Oncol 28:841–846PubMedCrossRef

32.

Hauser C, Katz SI (1988) Activation and expansion of hapten- and protein-specific T helper cells from nonsensitized mice. Proc Natl Acad Sci U S A 85:5625–5628PubMedPubMedCentralCrossRef

33.

Hauser C, Yokoyama WM, Katz SI (1989) Characterization of primary T helper cell activation and T helper cell lines stimulated by hapten-modified, cultured Langerhans cells. J Invest Dermatol 93:649–655PubMedCrossRef

34.

Heath WR, Carbone FR (2009) Dendritic cell subsets in primary and secondary T cell responses at body surfaces. Nat Immunol 10:1237–1244PubMedCrossRef

35.

Hirahara K, Ghoreschi K, Laurence A et al (2012) Signal transduction pathways and transcriptional regulation in Th17 cell differentiation. Cytokine Growth Factor Rev 21:425–434CrossRef

36.

Hoffman HM, Mueller JL, Broide DH et al (2001) Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet 29:301–305PubMedPubMedCentralCrossRef

37.

Igyarto BZ, Kaplan DH (2013) Antigen presentation by Langerhans cells. Curr Opin Immunol 25:115–119PubMedPubMedCentralCrossRef

38.

Jakob T, Saitoh A, Udey MC (1997) E-cadherin-mediated adhesion involving Langerhans cell-like dendritic cells expanded from murine fetal skin. J Immunol 159:2693–2701PubMed

39.

Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11:373–384PubMedCrossRef

40.

Kopp T, Riedl E, Bangert C et al (2015) Clinical improvement in psoriasis with specific targeting of interleukin-23. Nature 521:222–226PubMedCrossRef

41.

Langley RG, Lebwohl M, Krueger GG et al (2015) Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up. Br J Dermatol 172:1371–1383PubMedCrossRef

42.

Lauterbach H, Bathke B, Gilles S et al (2010) Mouse CD8alpha + DCs and human BDCA3+ DCs are major producers of IFN-lambda in response to poly IC. J Exp Med 207:2703–2717PubMedPubMedCentralCrossRef

43.

Lee HH, Song IH, Friedrich M et al (2007) Cutaneous side-effects in patients with rheumatic diseases during application of tumour necrosis factor-alpha antagonists. Br J Dermatol 156:486–491PubMedCrossRef

44.

Leonardi C, Matheson R, Zachariae C et al (2012) Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med 366:1190–1199PubMedCrossRef

45.

Li P, Allen H, Banerjee S et al (1995) Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock. Cell 80:401–411PubMedCrossRef

46.

Lopez-Olivo MA, Tayar JH, Martinez-Lopez JA et al (2012) Risk of malignancies in patients with rheumatoid arthritis treated with biologic therapy: a meta-analysis. JAMA 308:898–908PubMedCrossRef

47.

Luckey U, Schmidt T, Pfender N et al (2012) Crosstalk of regulatory T cells and tolerogenic dendritic cells prevents contact allergy in subjects with low zone tolerance. J Allergy Clin Immunol 130(781–797):e711

48.

Malissen B, Tamoutounour S, Henri S (2014) The origins and functions of dendritic cells and macrophages in the skin. Nat Rev Immunol 14:417–428PubMedCrossRef

49.

Mariathasan S, Weiss DS, Newton K et al (2006) Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440:228–232PubMedCrossRef

50.

Mocikat R, Braumuller H, Gumy A et al (2003) Natural killer cells activated by MHC class I(low) targets prime dendritic cells to induce protective CD8 T cell responses. Immunity 19:561–569PubMedCrossRef

51.

O’shea JJ, Paul WE (2010) Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 327:1098–1102PubMedPubMedCentralCrossRef

52.

Pasparakis M, Haase I, Nestle FO (2014) Mechanisms regulating skin immunity and inflammation. Nat Rev Immunol 14:289–301PubMedCrossRef

53.

Reich K, Nestle FO, Papp K et al (2005) Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 366:1367–1374PubMedCrossRef

54.

Reich K, Langley RG, Papp KA et al (2011) A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis. N Engl J Med 365:1586–1596PubMedCrossRef

55.

Rocken M, Muller KM, Saurat JH et al (1992) Central role for TCR/CD3 ligation in the differentiation of CD4+ T cells toward A Th1 or Th2 functional phenotype. J Immunol 148:47–54PubMed

56.

Rocken M, Saurat JH, Hauser C (1992) A common precursor for CD4+ T cells producing IL-2 or IL-4. J Immunol 148:1031–1036PubMed

57.

Romani N, Clausen BE, Stoitzner P (2010) Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunol Rev 234:120–141PubMedPubMedCentralCrossRef

58.

Salmon-Ceron D, Tubach F, Lortholary O et al (2011) Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry. Ann Rheum Dis 70:616–623PubMedCrossRef

59.

Schuler G, Steinman RM (1997) Dendritic cells as adjuvants for immune-mediated resistance to tumors. J Exp Med 186:1183–1187PubMedPubMedCentralCrossRef

60.

Singh JA, Cameron C, Noorbaloochi S et al (2015) Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis. Lancet 386:258–265PubMedCrossRef

61.

Skabytska Y, Wolbing F, Gunther C et al (2014) Cutaneous innate immune sensing of Toll-like receptor 2–6 ligands suppresses T cell immunity by inducing myeloid-derived suppressor cells. Immunity 41:762–775PubMedCrossRef

62.

Sollberger G, Strittmatter GE, Grossi S et al (2015) Caspase-1 activity is required for UVB-induced apoptosis of human keratinocytes. J Invest Dermatol 135:1395–1404PubMedCrossRef

63.

Staehli F, Ludigs K, Heinz LX et al (2012) NLRC5 deficiency selectively impairs MHC class I-dependent lymphocyte killing by cytotoxic T cells. J Immunol 188:3820–3828PubMedCrossRef

64.

Tattoli I, Travassos LH, Carneiro LA et al (2007) The Nodosome: Nod1 and Nod2 control bacterial infections and inflammation. Semin Immunopathol 29:289–301PubMedCrossRef

65.

Thornberry NA, Bull HG, Calaycay JR et al (1992) A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356:768–774PubMedCrossRef

66.

Villanova F, Flutter B, Tosi I et al (2014) Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis. J Invest Dermatol 134:984–991PubMedPubMedCentralCrossRef

67.

Wollenberg A, Kraft S, Hanau D et al (1996) Immunomorphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema. J Invest Dermatol 106:446–453PubMedCrossRef

68.

Yang XP, Ghoreschi K, Steward-Tharp SM et al (2011) Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol 12:247–254PubMedPubMedCentralCrossRef

69.

Yao C, Zurawski SM, Jarrett ES et al. (2015) Skin dendritic cells induce follicular helper T cells and protective humoral immune responses. J Allergy Clin Immunol

70.

Yazdi AS, Guarda G, Riteau N et al (2010) Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1alpha and IL-1beta. Proc Natl Acad Sci U S A 107:19449–19454PubMedPubMedCentralCrossRef

71.

Zimmermann S, Egeter O, Hausmann S et al (1998) CpG oligodeoxynucleotides trigger protective and curative Th1 responses in lethal murine leishmaniasis. J Immunol 160:3627–3630PubMed

72.

Zuo X, Sun L, Yin X et al (2015) Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis. Nat Commun 6:6793PubMedPubMedCentralCrossRef

Titel: Cutaneous immunology: basics and new concepts
verfasst von: Amir S. Yazdi
Martin Röcken
Kamran Ghoreschi
Publikationsdatum: 01.01.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Seminars in Immunopathology / Ausgabe 1/2016
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-015-0545-x

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

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

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

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2016

Cutaneous dermatomyositis in the era of biologicals

The role of innate immune signaling in the pathogenesis of atopic dermatitis and consequences for treatments

The continuing evolution of targeted therapy for inflammatory skin disease

Lupus erythematosus revisited

Update on psoriasis immunopathogenesis and targeted immunotherapy