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Erschienen in: Seminars in Immunopathology 6/2020

20.11.2020 | Review

Control of immunity by glucocorticoids in health and disease

verfasst von: Akihiro Shimba, Koichi Ikuta

Erschienen in: Seminars in Immunopathology | Ausgabe 6/2020

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Abstract

Animals receive environmental stimuli from neural signals in order to produce hormones that control immune responses. Glucocorticoids (GCs) are a group of steroid hormones produced in the adrenal cortex and well-known mediators for the nervous and immune systems. GC secretion is induced by circadian rhythm and stress, and plasma GC levels are high at the active phase of animals and under stress condition. Clinically, GCs are used for allergies, autoimmunity, and chronic inflammation, because they have strong anti-inflammatory effects and induce the apoptosis of lymphocytes. Glucocorticoid receptor (GR) acts as a transcription factor and represses the expression of inflammatory cytokines, chemokines, and prostaglandins by binding to its motif, glucocorticoid-response element, or to other transcription factors. In mice, GR suppresses the antigen-stimulated inflammation mediated by macrophages, dendritic cells, and epithelial cells, and impairs cytotoxic immune responses by downregulating interferon-γ production and inhibiting the development of type-1 helper T cells, CD8+ T cells, and natural killer cells. These immune inhibitory effects prevent lethality by excessive inflammation, but at the same time increase the susceptibility to infection and cancer. GCs can also activate the immune system. The circadian cycle of GC secretion controls the diurnal oscillations of the distribution and response of T cells, thus supporting T cell maintenance and effective immune protection against infection. Moreover, several reports have shown that GR has the potential to enhance the activities of Th2, Th17, and immunoglobulin-producing B cells. Stress has two different effects on immune responses: immune suppression to cause mortality by infection and cancer, and excessive immune activation to induce chronic inflammation and autoimmune disease. Consistently, stress-induced GCs strongly suppress cell-mediated immunity and cause viral infection and tumor development. They may also enhance the development of pathogenic helper T cells and cause tissue damage through neural and intestinal inflammation. Past studies have reported the positive and negative effects of GCs on the immune system. These opposing properties of GCs may regulate the immune balance between the responsiveness to antigens and excessive inflammation in steady-state and stress conditions.
Literatur
1.
Zurück zum Zitat Cain DW, Cidlowski JA (2017) Immune regulation by glucocorticoids. Nat Rev Immunol 17:233–247PubMed Cain DW, Cidlowski JA (2017) Immune regulation by glucocorticoids. Nat Rev Immunol 17:233–247PubMed
2.
Zurück zum Zitat Vandevyver S, Dejager L, Libert C (2014) Comprehensive overview of the structure and regulation of the glucocorticoid receptor. Endocr Rev 35:671–693PubMed Vandevyver S, Dejager L, Libert C (2014) Comprehensive overview of the structure and regulation of the glucocorticoid receptor. Endocr Rev 35:671–693PubMed
3.
Zurück zum Zitat Almawi WY, Beyhum HN, Rahme AA, Rieder MJ (1996) Regulation of cytokine and cytokine receptor expression by glucocorticoids. J Leukoc Biol 60:563–572PubMed Almawi WY, Beyhum HN, Rahme AA, Rieder MJ (1996) Regulation of cytokine and cytokine receptor expression by glucocorticoids. J Leukoc Biol 60:563–572PubMed
4.
Zurück zum Zitat Kunicka JE, Talle MA, Denhardt GH, Brown M, Prince LA, Goldstein G (1993) Immunosuppression by glucocorticoids: inhibition of production of multiple lymphokines by in vivo administration of dexamethasone. Cell Immunol 149:39–49PubMed Kunicka JE, Talle MA, Denhardt GH, Brown M, Prince LA, Goldstein G (1993) Immunosuppression by glucocorticoids: inhibition of production of multiple lymphokines by in vivo administration of dexamethasone. Cell Immunol 149:39–49PubMed
5.
Zurück zum Zitat Fushimi T, Shimura S, Suzuki S, Saitoh H, Okayama H, Shirato K (1998) Suppression of gene expression and production of interleukin 13 by dexamethasone in human peripheral blood mononuclear cells. Tohoku J Exp Med 185:157–160PubMed Fushimi T, Shimura S, Suzuki S, Saitoh H, Okayama H, Shirato K (1998) Suppression of gene expression and production of interleukin 13 by dexamethasone in human peripheral blood mononuclear cells. Tohoku J Exp Med 185:157–160PubMed
6.
Zurück zum Zitat Rolfe FG, Hughes JM, Armour CL, Sewell WA (1992) Inhibition of interleukin-5 gene expression by dexamethasone. Immunology 77:494–499PubMedPubMedCentral Rolfe FG, Hughes JM, Armour CL, Sewell WA (1992) Inhibition of interleukin-5 gene expression by dexamethasone. Immunology 77:494–499PubMedPubMedCentral
7.
Zurück zum Zitat Brewer JA, Kanagawa O, Sleckman BP, Muglia LJ (2002) Thymocyte apoptosis induced by T cell activation is, mediated by glucocorticoids in vivo. J Immunol 169:1837–1843PubMed Brewer JA, Kanagawa O, Sleckman BP, Muglia LJ (2002) Thymocyte apoptosis induced by T cell activation is, mediated by glucocorticoids in vivo. J Immunol 169:1837–1843PubMed
8.
Zurück zum Zitat Surjit M, Ganti KP, Mukherji A, Ye T, Hua G, Metzger D, Li M, Chambon P (2011) Widespread negative response elements mediate direct repression by agonist-liganded glucocorticoid receptor. Cell 145:224–241PubMed Surjit M, Ganti KP, Mukherji A, Ye T, Hua G, Metzger D, Li M, Chambon P (2011) Widespread negative response elements mediate direct repression by agonist-liganded glucocorticoid receptor. Cell 145:224–241PubMed
9.
Zurück zum Zitat Auphan N, Didonato JA, Rosette C, Helmberg A, Karin M (1995) Immunosuppression by glucocorticoids: inhibition of NF-kB activity through induction of IkB synthesis. Science 270:286–290PubMed Auphan N, Didonato JA, Rosette C, Helmberg A, Karin M (1995) Immunosuppression by glucocorticoids: inhibition of NF-kB activity through induction of IkB synthesis. Science 270:286–290PubMed
10.
Zurück zum Zitat Abraham SM, Lawrence T, Kleiman A, Warden P, Medghalchi M, Tuckermann J, Saklatvala J, Clark AR (2006) Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1. J Exp Med 203:1883–1889PubMedPubMedCentral Abraham SM, Lawrence T, Kleiman A, Warden P, Medghalchi M, Tuckermann J, Saklatvala J, Clark AR (2006) Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1. J Exp Med 203:1883–1889PubMedPubMedCentral
11.
Zurück zum Zitat Berrebi D, Bruscoli S, Cohen N, Foussat A, Migliorati G, Bouchet-Delbos L, Maillot MC, Portier A, Couderc J, Galanaud P, Peuchmaur M, Riccardi C, Emilie D (2003) Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10. Blood 101:729–738PubMed Berrebi D, Bruscoli S, Cohen N, Foussat A, Migliorati G, Bouchet-Delbos L, Maillot MC, Portier A, Couderc J, Galanaud P, Peuchmaur M, Riccardi C, Emilie D (2003) Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10. Blood 101:729–738PubMed
12.
Zurück zum Zitat Smoak K, Cidlowski JA (2006) Glucocorticoids regulate tristetraprolin synthesis and posttranscriptionally regulate tumor necrosis factor alpha inflammatory signaling. Mol Cell Biol 2006(26):9126–9135 Smoak K, Cidlowski JA (2006) Glucocorticoids regulate tristetraprolin synthesis and posttranscriptionally regulate tumor necrosis factor alpha inflammatory signaling. Mol Cell Biol 2006(26):9126–9135
13.
Zurück zum Zitat Tobler A, Meier R, Seitz M, Dewald B, Baggiolini M, Fey MF (1992) Glucocorticoids downregulate gene expression of GM-CSF, NAP-1/IL-8, and IL-6, but not of M-CSF in human fibroblasts. Blood 79:45–51PubMed Tobler A, Meier R, Seitz M, Dewald B, Baggiolini M, Fey MF (1992) Glucocorticoids downregulate gene expression of GM-CSF, NAP-1/IL-8, and IL-6, but not of M-CSF in human fibroblasts. Blood 79:45–51PubMed
14.
Zurück zum Zitat Scheinman RI, Gualberto A, Jewell CM, Cidlowski JA, Baldwin AS (1995) Characterization of mechanisms involved in transrepression of NF-kB by activated glucocorticoid receptors. Mol Cell Biol 15:943–953PubMedPubMedCentral Scheinman RI, Gualberto A, Jewell CM, Cidlowski JA, Baldwin AS (1995) Characterization of mechanisms involved in transrepression of NF-kB by activated glucocorticoid receptors. Mol Cell Biol 15:943–953PubMedPubMedCentral
15.
Zurück zum Zitat Jonat C, Rahmsdorf HJ, Park KK, Cato ACB, Gebel S, Ponta H, Herrlich P (1990) Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell 62:1189–1204PubMed Jonat C, Rahmsdorf HJ, Park KK, Cato ACB, Gebel S, Ponta H, Herrlich P (1990) Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell 62:1189–1204PubMed
16.
Zurück zum Zitat Newton R, Kuitert LM, Slater DM, Adcock IM, Barnes PJ (1996) Cytokine induction of cytosolic phospholipase A2 and cyclooxygenase-2 mRNA is suppressed by glucocorticoids in human epithelial cells. Life Sci 60:67–78 Newton R, Kuitert LM, Slater DM, Adcock IM, Barnes PJ (1996) Cytokine induction of cytosolic phospholipase A2 and cyclooxygenase-2 mRNA is suppressed by glucocorticoids in human epithelial cells. Life Sci 60:67–78
17.
Zurück zum Zitat Lin LL, Lin AY, Dewitt DL (1992) Interleukin-1a induces the accumulation of cytosolic phospholipase A2 and the release of prostaglandin E2 in human fibroblasts. J Biol Chem 267:23451–23454PubMed Lin LL, Lin AY, Dewitt DL (1992) Interleukin-1a induces the accumulation of cytosolic phospholipase A2 and the release of prostaglandin E2 in human fibroblasts. J Biol Chem 267:23451–23454PubMed
18.
Zurück zum Zitat Hoeck WG, Ramesha CS, Chang DJ, Fan N, Heller RA (1993) Cytoplasmic phospholipase A2 activity and gene expression are stimulated by tumor necrosis factor: dexamethasone blocks the induced synthesis. Proc Natl Acad Sci U S A 90:4475–4479PubMedPubMedCentral Hoeck WG, Ramesha CS, Chang DJ, Fan N, Heller RA (1993) Cytoplasmic phospholipase A2 activity and gene expression are stimulated by tumor necrosis factor: dexamethasone blocks the induced synthesis. Proc Natl Acad Sci U S A 90:4475–4479PubMedPubMedCentral
19.
Zurück zum Zitat Masferrer JL, Zweifel BS, Seibert K, Needleman P (1990) Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice. J Clin Invest 1990(86):1375–1379 Masferrer JL, Zweifel BS, Seibert K, Needleman P (1990) Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice. J Clin Invest 1990(86):1375–1379
20.
Zurück zum Zitat Rider LG, Hirasawa N, Santini F, Beaven MA (1996) Activation of the mitogen activated protein kinase cascade is suppressed by low concentrations of dexamethasone in mast cells. J Immunol 157:2374–2380PubMed Rider LG, Hirasawa N, Santini F, Beaven MA (1996) Activation of the mitogen activated protein kinase cascade is suppressed by low concentrations of dexamethasone in mast cells. J Immunol 157:2374–2380PubMed
21.
Zurück zum Zitat Kleiman A, Hubner S, Parkitna JMR, Neumann A, Hofer S, Weigand MA, Bauer M, Schmid W, Schutz G, Libert C, Reichardt HM, Tuckermann JP (2012) Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages. FASEB J 26:722–729PubMed Kleiman A, Hubner S, Parkitna JMR, Neumann A, Hofer S, Weigand MA, Bauer M, Schmid W, Schutz G, Libert C, Reichardt HM, Tuckermann JP (2012) Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages. FASEB J 26:722–729PubMed
22.
Zurück zum Zitat Tuckermann JP, Kleiman A, Moriggl R, Spanbroek R, Neumann A, Illing A, Clausen BE, Stride B, Forster I, Habenicht AJ, Reichardt HM, Tronche F, Schmid W, Schutz G (2007) Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy. J Clin Invest 117:1381–1390PubMedPubMedCentral Tuckermann JP, Kleiman A, Moriggl R, Spanbroek R, Neumann A, Illing A, Clausen BE, Stride B, Forster I, Habenicht AJ, Reichardt HM, Tronche F, Schmid W, Schutz G (2007) Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy. J Clin Invest 117:1381–1390PubMedPubMedCentral
23.
Zurück zum Zitat Klassen C, Karabinskaya A, Dejager L, Vettorazzi S, Van Moorleghem J, Luhder F, Meijsing SH, Tuckermann JP, Bohnenberger H, Libert C, Reichardt HM (2017) Airway epithelial cells are crucial targets of glucocorticoids in a mouse model of allergic asthma. J Immunol 199:48–61PubMed Klassen C, Karabinskaya A, Dejager L, Vettorazzi S, Van Moorleghem J, Luhder F, Meijsing SH, Tuckermann JP, Bohnenberger H, Libert C, Reichardt HM (2017) Airway epithelial cells are crucial targets of glucocorticoids in a mouse model of allergic asthma. J Immunol 199:48–61PubMed
24.
Zurück zum Zitat Baschant U, Frappart L, Rauchhaus U, Bruns L, Reichardt HM, Kamradt T, Brauer R, Tuckermann JP (2011) Glucocorticoid therapy of antigen induced arthritis depends on the dimerized glucocorticoid receptor in T cells. Proc Natl Acad Sci U S A 108:19317–19322PubMedPubMedCentral Baschant U, Frappart L, Rauchhaus U, Bruns L, Reichardt HM, Kamradt T, Brauer R, Tuckermann JP (2011) Glucocorticoid therapy of antigen induced arthritis depends on the dimerized glucocorticoid receptor in T cells. Proc Natl Acad Sci U S A 108:19317–19322PubMedPubMedCentral
25.
Zurück zum Zitat Siegel RM, Katsumata M, Miyashita T, Louie DC, Greene MI, Reed JC (1992) Inhibition of thymocyte apoptosis and negative antigenic selection in Bcl-2 transgenic mice. Proc Natl Acad Sci U S A 89:7003–7007PubMedPubMedCentral Siegel RM, Katsumata M, Miyashita T, Louie DC, Greene MI, Reed JC (1992) Inhibition of thymocyte apoptosis and negative antigenic selection in Bcl-2 transgenic mice. Proc Natl Acad Sci U S A 89:7003–7007PubMedPubMedCentral
26.
Zurück zum Zitat Cecconi F, Alvarez-Bolado G, Meyer BI, Roth KA, Gruss P (1998) Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development. Cell 94:727–737PubMed Cecconi F, Alvarez-Bolado G, Meyer BI, Roth KA, Gruss P (1998) Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development. Cell 94:727–737PubMed
27.
Zurück zum Zitat Yoshida H, Kong YY, Yoshida R, Elia AJ, Hakem A, Hakem R, Penninger JM, Mak TW (1998) Apaf1 is required for mitochondrial pathways of apoptosis and brain development. Cell 94:739–750PubMed Yoshida H, Kong YY, Yoshida R, Elia AJ, Hakem A, Hakem R, Penninger JM, Mak TW (1998) Apaf1 is required for mitochondrial pathways of apoptosis and brain development. Cell 94:739–750PubMed
28.
Zurück zum Zitat Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS, Elia A, de la Pompa JL, Kagi D, Khoo W, Potter J, Yoshida R, Kaufman SA, Lowe SW, Penninger JM, Mak TW (1998) Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 94:339–352PubMed Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS, Elia A, de la Pompa JL, Kagi D, Khoo W, Potter J, Yoshida R, Kaufman SA, Lowe SW, Penninger JM, Mak TW (1998) Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 94:339–352PubMed
29.
Zurück zum Zitat Kuida K, Haydar TF, Kuan CY, Gu Y, Taya C, Karasuyama H, Su MSS, Rakic P, Flavell RA (1998) Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94:325–337PubMed Kuida K, Haydar TF, Kuan CY, Gu Y, Taya C, Karasuyama H, Su MSS, Rakic P, Flavell RA (1998) Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94:325–337PubMed
30.
Zurück zum Zitat Dieken ES, Miesfeld RL (1992) Transcriptional transactivation functions localized to the glucocorticoid receptor N terminus are necessary for steroid induction of lymphocyte apoptosis. Mol Cell Biol 12:589–597PubMedPubMedCentral Dieken ES, Miesfeld RL (1992) Transcriptional transactivation functions localized to the glucocorticoid receptor N terminus are necessary for steroid induction of lymphocyte apoptosis. Mol Cell Biol 12:589–597PubMedPubMedCentral
31.
Zurück zum Zitat Gibbs J, Ince L, Matthews L, Mei JJ, Bell T, Yang N, Saer B, Begley N, Poolman T, Pariollaud M, Farrow S, DeMayo F, Hussell T, Worthen GS, Ray D, Loudon A (2014) An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action. Nat Med 20:919–926PubMedPubMedCentral Gibbs J, Ince L, Matthews L, Mei JJ, Bell T, Yang N, Saer B, Begley N, Poolman T, Pariollaud M, Farrow S, DeMayo F, Hussell T, Worthen GS, Ray D, Loudon A (2014) An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action. Nat Med 20:919–926PubMedPubMedCentral
32.
Zurück zum Zitat Ince LM, Zhang ZG, Beesley S, Vonslow RM, Saer B, Matthews LC, Begley N, Gibbs JE, Ray DW, Loudon ASI (2019) Circadian variation in pulmonary inflammatory responses is independent of rhythmic glucocorticoid signaling in airway epithelial cells. FASEB J 33:126–139PubMed Ince LM, Zhang ZG, Beesley S, Vonslow RM, Saer B, Matthews LC, Begley N, Gibbs JE, Ray DW, Loudon ASI (2019) Circadian variation in pulmonary inflammatory responses is independent of rhythmic glucocorticoid signaling in airway epithelial cells. FASEB J 33:126–139PubMed
33.
Zurück zum Zitat Bhattacharyya S, Brown DE, Brewer JA, Vogt SK, Muglia LJ (2007) Macrophage glucocorticoid receptors regulate toll-like receptor 4-mediated inflammatory responses by selective inhibition of p38 MAP kinase. Blood 109:4313–4319PubMedPubMedCentral Bhattacharyya S, Brown DE, Brewer JA, Vogt SK, Muglia LJ (2007) Macrophage glucocorticoid receptors regulate toll-like receptor 4-mediated inflammatory responses by selective inhibition of p38 MAP kinase. Blood 109:4313–4319PubMedPubMedCentral
34.
Zurück zum Zitat Li CYC, Munitic I, Mittelstadt PR, Castro E, Ashwell JD (2015) Suppression of dendritic cell-derived IL-12 by endogenous glucocorticoids is protective in LPS-induced sepsis. PLoS Biol 13:e1002269PubMedPubMedCentral Li CYC, Munitic I, Mittelstadt PR, Castro E, Ashwell JD (2015) Suppression of dendritic cell-derived IL-12 by endogenous glucocorticoids is protective in LPS-induced sepsis. PLoS Biol 13:e1002269PubMedPubMedCentral
35.
Zurück zum Zitat Quatrini L, Wieduwild E, Guia S, Bernat C, Glaichenhaus N, Vivier E, Ugolini S (2017) Host resistance to endotoxic shock requires the neuroendocrine regulation of group 1 innate lymphoid cells. J Exp Med 214:3531–3541PubMedPubMedCentral Quatrini L, Wieduwild E, Guia S, Bernat C, Glaichenhaus N, Vivier E, Ugolini S (2017) Host resistance to endotoxic shock requires the neuroendocrine regulation of group 1 innate lymphoid cells. J Exp Med 214:3531–3541PubMedPubMedCentral
36.
Zurück zum Zitat Quatrini L, Wieduwild E, Escaliere B, Filtjens J, Chasson L, Laprie C, Vivier E, Ugolini S (2018) Endogenous glucocorticoids control host resistance to viral infection through the tissue-specific regulation of PD-1 expression on NK cells. Nat Immunol 19:954–962PubMedPubMedCentral Quatrini L, Wieduwild E, Escaliere B, Filtjens J, Chasson L, Laprie C, Vivier E, Ugolini S (2018) Endogenous glucocorticoids control host resistance to viral infection through the tissue-specific regulation of PD-1 expression on NK cells. Nat Immunol 19:954–962PubMedPubMedCentral
37.
Zurück zum Zitat Chen LY, Jondal M, Yakimchuk K (2018) Regulatory effects of dexamethasone on NK and T cell immunity. Inflammopharmacology 26:1331–1338PubMed Chen LY, Jondal M, Yakimchuk K (2018) Regulatory effects of dexamethasone on NK and T cell immunity. Inflammopharmacology 26:1331–1338PubMed
38.
Zurück zum Zitat Brewer JA, Khor B, Vogt SK, Muglia LM, Fujiwara H, Haegele KE, Sleckman BP, Muglia LJ (2003) T cell glucocorticoid receptor is required to suppress COX-2-mediated lethal immune activation. Nat Med 9:1318–1322PubMed Brewer JA, Khor B, Vogt SK, Muglia LM, Fujiwara H, Haegele KE, Sleckman BP, Muglia LJ (2003) T cell glucocorticoid receptor is required to suppress COX-2-mediated lethal immune activation. Nat Med 9:1318–1322PubMed
39.
Zurück zum Zitat Wu CY, Wang KN, McDyer JF, Seder RA (1998) Prostaglandin E2 and dexamethasone inhibit IL-12 receptor expression and IL-12 responsiveness. J Immunol 161:2723–2730PubMed Wu CY, Wang KN, McDyer JF, Seder RA (1998) Prostaglandin E2 and dexamethasone inhibit IL-12 receptor expression and IL-12 responsiveness. J Immunol 161:2723–2730PubMed
40.
Zurück zum Zitat Franchimont D, Galon J, Gadina M, Visconti R, Zhou YJ, Aringer M, Frucht DM, Chrousos GP, O’Shea JJ (2000) Inhibition of Th1 immune response by glucocorticoids, dexamethasone selectively inhibits IL-12-induced Stat4 phosphorylation in T lymphocytes. J Immunol 164:1768–1774PubMed Franchimont D, Galon J, Gadina M, Visconti R, Zhou YJ, Aringer M, Frucht DM, Chrousos GP, O’Shea JJ (2000) Inhibition of Th1 immune response by glucocorticoids, dexamethasone selectively inhibits IL-12-induced Stat4 phosphorylation in T lymphocytes. J Immunol 164:1768–1774PubMed
41.
Zurück zum Zitat Liberman AC, Refojo D, Druker J, Toscano M, Rein T, Holsboer F, Arzt E (2007) The activated glucocorticoid receptor inhibits the transcription factor T-bet by direct protein-protein interaction. FASEB J 21:1177–1188PubMed Liberman AC, Refojo D, Druker J, Toscano M, Rein T, Holsboer F, Arzt E (2007) The activated glucocorticoid receptor inhibits the transcription factor T-bet by direct protein-protein interaction. FASEB J 21:1177–1188PubMed
42.
Zurück zum Zitat Kugler DG, Mittelstadt PR, Ashwell JD, Sher A, Jankovic D (2013) CD4+ T cells are trigger and target of the glucocorticoid response that prevents lethal immunopathology in toxoplasma infection. J Exp Med 210:1919–1927PubMedPubMedCentral Kugler DG, Mittelstadt PR, Ashwell JD, Sher A, Jankovic D (2013) CD4+ T cells are trigger and target of the glucocorticoid response that prevents lethal immunopathology in toxoplasma infection. J Exp Med 210:1919–1927PubMedPubMedCentral
43.
Zurück zum Zitat Franchimont D, Galon J, Vacchio MS, Fan S, Visconti R, Frucht DM, Geenen V, Chrousos GP, Ashwell JD, O’Shea JJ (2002) Positive effects of glucocorticoids on T cell function by up-regulation of IL-7 receptor α. J Immunol 168:2212–2218PubMed Franchimont D, Galon J, Vacchio MS, Fan S, Visconti R, Frucht DM, Geenen V, Chrousos GP, Ashwell JD, O’Shea JJ (2002) Positive effects of glucocorticoids on T cell function by up-regulation of IL-7 receptor α. J Immunol 168:2212–2218PubMed
44.
Zurück zum Zitat Diefenbach A, Colonna M, Koyasu S (2014) Development, differentiation, and diversity of innate lymphoid cells. Immunity 41:354–365PubMedPubMedCentral Diefenbach A, Colonna M, Koyasu S (2014) Development, differentiation, and diversity of innate lymphoid cells. Immunity 41:354–365PubMedPubMedCentral
45.
Zurück zum Zitat Mazzucchelli R, Durum SK (2007) Interleukin-7 receptor expression: intelligent design. Nat Rev Immunol 7:144–154PubMed Mazzucchelli R, Durum SK (2007) Interleukin-7 receptor expression: intelligent design. Nat Rev Immunol 7:144–154PubMed
46.
Zurück zum Zitat Tani-ichi S, Shimba A, Wagatsuma K, Miyachi H, Kitano S, Imai K, Hara T, Ikuta K (2013) Interleukin-7 receptor controls development and maturation of late stages of thymocyte subpopulations. Proc Natl Acad Sci U S A 110:612–617PubMed Tani-ichi S, Shimba A, Wagatsuma K, Miyachi H, Kitano S, Imai K, Hara T, Ikuta K (2013) Interleukin-7 receptor controls development and maturation of late stages of thymocyte subpopulations. Proc Natl Acad Sci U S A 110:612–617PubMed
47.
Zurück zum Zitat Lee HC, Shibata H, Ogawa S, Maki K, Ikuta K (2005) Transcriptional regulation of the mouse IL-7 receptor α promoter by glucocorticoid receptor. J Immunol 174:7800–7806PubMed Lee HC, Shibata H, Ogawa S, Maki K, Ikuta K (2005) Transcriptional regulation of the mouse IL-7 receptor α promoter by glucocorticoid receptor. J Immunol 174:7800–7806PubMed
48.
Zurück zum Zitat Abe A, Tani-ichi S, Shitara S, Cui G, Yamada H, Miyachi H, Kitano S, Hara T, Abe R, Yoshikai Y, Ikuta K (2015) An enhancer of the IL-7 receptor α-chain locus controls IL-7 receptor expression and maintenance of peripheral T cells. J Immunol 195:3129–3138PubMed Abe A, Tani-ichi S, Shitara S, Cui G, Yamada H, Miyachi H, Kitano S, Hara T, Abe R, Yoshikai Y, Ikuta K (2015) An enhancer of the IL-7 receptor α-chain locus controls IL-7 receptor expression and maintenance of peripheral T cells. J Immunol 195:3129–3138PubMed
49.
Zurück zum Zitat Shimba A, Cui GW, Tani-ichi S, Ogawa M, Abe S, Okazaki F, Kitano S, Miyachi H, Yamada H, Hara T, Yoshikai Y, Nagasawa T, Schutz G, Ikuta K (2018) Glucocorticoids drive diurnal oscillations in T cell distribution and responses by inducing interleukin-7 receptor and CXCR4. Immunity 48:286–298PubMed Shimba A, Cui GW, Tani-ichi S, Ogawa M, Abe S, Okazaki F, Kitano S, Miyachi H, Yamada H, Hara T, Yoshikai Y, Nagasawa T, Schutz G, Ikuta K (2018) Glucocorticoids drive diurnal oscillations in T cell distribution and responses by inducing interleukin-7 receptor and CXCR4. Immunity 48:286–298PubMed
50.
Zurück zum Zitat Haus E, Smolensky MH (1999) Biologic rhythms in the immune system. Chronobiol Int 16:581–622PubMed Haus E, Smolensky MH (1999) Biologic rhythms in the immune system. Chronobiol Int 16:581–622PubMed
51.
Zurück zum Zitat Dimitrov S, Benedict C, Heutling D, Westermann J, Born J, Lange T (2009) Cortisol and epinephrine control opposing circadian rhythms in T cell subsets. Blood 113:5134–5143PubMedPubMedCentral Dimitrov S, Benedict C, Heutling D, Westermann J, Born J, Lange T (2009) Cortisol and epinephrine control opposing circadian rhythms in T cell subsets. Blood 113:5134–5143PubMedPubMedCentral
52.
Zurück zum Zitat Jourdan P, Vendrell JP, Huguet MF, Segondy M, Bousquet J, Pene J, Yssel H (2000) Cytokines and cell surface molecules independently induce CXCR4 expression on CD4+ CCR7+ human memory T cells. J Immunol 165:716–724PubMed Jourdan P, Vendrell JP, Huguet MF, Segondy M, Bousquet J, Pene J, Yssel H (2000) Cytokines and cell surface molecules independently induce CXCR4 expression on CD4+ CCR7+ human memory T cells. J Immunol 165:716–724PubMed
53.
Zurück zum Zitat Curtis AM, Bellet MM, Sassone-Corsi P, O’Neill LAJ (2014) Circadian clock proteins and immunity. Immunity 40:178–186PubMed Curtis AM, Bellet MM, Sassone-Corsi P, O’Neill LAJ (2014) Circadian clock proteins and immunity. Immunity 40:178–186PubMed
54.
Zurück zum Zitat Suzuki K, Hayano Y, Nakai A, Furuta F, Noda M (2016) Adrenergic control of the adaptive immune response by diurnal lymphocyte recirculation through lymph nodes. J Exp Med 213:2567–2574PubMedPubMedCentral Suzuki K, Hayano Y, Nakai A, Furuta F, Noda M (2016) Adrenergic control of the adaptive immune response by diurnal lymphocyte recirculation through lymph nodes. J Exp Med 213:2567–2574PubMedPubMedCentral
55.
Zurück zum Zitat Druzd D, Matveeva O, Ince L, Harrison U, He WY, Schmal C, Herzel H, Tsang AH, Kawakami N, Leliavski A, Uhl O, Yao L, Sander LE, Chen CS, Kraus K, de Juan A, Hergenhan SM, Ehlers M, Koletzko B, Haas R, Solbach W, Oster H, Scheiermann C (2017) Lymphocyte circadian clocks control lymph node trafficking and adaptive immune responses. Immunity 46:120–132PubMedPubMedCentral Druzd D, Matveeva O, Ince L, Harrison U, He WY, Schmal C, Herzel H, Tsang AH, Kawakami N, Leliavski A, Uhl O, Yao L, Sander LE, Chen CS, Kraus K, de Juan A, Hergenhan SM, Ehlers M, Koletzko B, Haas R, Solbach W, Oster H, Scheiermann C (2017) Lymphocyte circadian clocks control lymph node trafficking and adaptive immune responses. Immunity 46:120–132PubMedPubMedCentral
56.
Zurück zum Zitat Erlacher M, Knoflach M, Stec IEM, Bock G, Wick G, Wiegers GJ (2005) TCR signaling inhibits glucocorticoid-induced apoptosis in murine thymocytes depending on the stage of development. Eur J Immunol 35:3287–3296PubMed Erlacher M, Knoflach M, Stec IEM, Bock G, Wick G, Wiegers GJ (2005) TCR signaling inhibits glucocorticoid-induced apoptosis in murine thymocytes depending on the stage of development. Eur J Immunol 35:3287–3296PubMed
57.
Zurück zum Zitat Bellet MM, Deriu E, Liu JZ, Grimaldi B, Blaschitz C, Zeller M, Edwards RA, Sahar S, Dandekar S, Baldi P, George MD, Raffatellu M, Sassone-Corsi P (2013) Circadian clock regulates the host response to Salmonella. Proc Natl Acad Sci U S A 110:9897–9902PubMedPubMedCentral Bellet MM, Deriu E, Liu JZ, Grimaldi B, Blaschitz C, Zeller M, Edwards RA, Sahar S, Dandekar S, Baldi P, George MD, Raffatellu M, Sassone-Corsi P (2013) Circadian clock regulates the host response to Salmonella. Proc Natl Acad Sci U S A 110:9897–9902PubMedPubMedCentral
58.
Zurück zum Zitat Grayson J, Dooley NJ, Koski IR, Blaese RM (1981) Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes. J Clin Invest 68:1539–1547PubMedPubMedCentral Grayson J, Dooley NJ, Koski IR, Blaese RM (1981) Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes. J Clin Invest 68:1539–1547PubMedPubMedCentral
59.
Zurück zum Zitat Lechner O, Wiegers GJ, Oliveira-dos-Santos AJ, Dietrich H, Recheis H, Waterman M, Boyd R, Wick G (2000) Glucocorticoid production in the murine thymus. Eur J Immunol 30:337–346PubMed Lechner O, Wiegers GJ, Oliveira-dos-Santos AJ, Dietrich H, Recheis H, Waterman M, Boyd R, Wick G (2000) Glucocorticoid production in the murine thymus. Eur J Immunol 30:337–346PubMed
60.
Zurück zum Zitat Cima I, Corazza N, Dick B, Fuhrer A, Herren S, Jakob S, Ayuni E, Mueller C, Brunner T (2004) Intestinal epithelial cells synthesize glucocorticoids and regulate T cell activation. J Exp Med 200:1635–1646PubMedPubMedCentral Cima I, Corazza N, Dick B, Fuhrer A, Herren S, Jakob S, Ayuni E, Mueller C, Brunner T (2004) Intestinal epithelial cells synthesize glucocorticoids and regulate T cell activation. J Exp Med 200:1635–1646PubMedPubMedCentral
61.
Zurück zum Zitat Mukherji A, Kobiita A, Ye T, Chambon P (2013) Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRs. Cell 153:812–827PubMed Mukherji A, Kobiita A, Ye T, Chambon P (2013) Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRs. Cell 153:812–827PubMed
62.
Zurück zum Zitat Mittelstadt PR, Monteiro JP, Ashwell JD (2012) Thymocyte responsiveness to endogenous glucocorticoids is required for immunological fitness. J Clin Invest 122:2384–2394PubMedPubMedCentral Mittelstadt PR, Monteiro JP, Ashwell JD (2012) Thymocyte responsiveness to endogenous glucocorticoids is required for immunological fitness. J Clin Invest 122:2384–2394PubMedPubMedCentral
63.
Zurück zum Zitat Cain DW, Bortner CD, Diaz-Jimenez D, Petrillo MG, Gruver-Yates A, Cidlowski JA (2020) Murine glucocorticoid receptors orchestrate B cell migration selectively between bone marrow and blood. J Immunol 205:619–629PubMed Cain DW, Bortner CD, Diaz-Jimenez D, Petrillo MG, Gruver-Yates A, Cidlowski JA (2020) Murine glucocorticoid receptors orchestrate B cell migration selectively between bone marrow and blood. J Immunol 205:619–629PubMed
64.
Zurück zum Zitat Elenkov IJ (2004) Glucocorticoids and the Th1/Th2 balance. Ann N Y Acad Sci 1024:138–146PubMed Elenkov IJ (2004) Glucocorticoids and the Th1/Th2 balance. Ann N Y Acad Sci 1024:138–146PubMed
65.
Zurück zum Zitat Blotta MH, DeKruyff RH, Umetsu DT (1997) Corticosteroids inhibit IL-12 production in human monocytes and enhance their capacity to induce IL-4 synthesis in CD4+ lymphocytes. J Immunol 158:5589–5595PubMed Blotta MH, DeKruyff RH, Umetsu DT (1997) Corticosteroids inhibit IL-12 production in human monocytes and enhance their capacity to induce IL-4 synthesis in CD4+ lymphocytes. J Immunol 158:5589–5595PubMed
66.
Zurück zum Zitat Kodama M, Takahashi H, Iwagaki H, Itoh H, Morichika T, Yoshida A, Yoshioka H, Morimoto Y, Nishibori M, Tanaka N (2002) Effect of steroids on lipopolysaccharide/interleukin-2 induced interleukin-18 production in peripheral blood mononuclear cells. J Int Med Res 30:144–160PubMed Kodama M, Takahashi H, Iwagaki H, Itoh H, Morichika T, Yoshida A, Yoshioka H, Morimoto Y, Nishibori M, Tanaka N (2002) Effect of steroids on lipopolysaccharide/interleukin-2 induced interleukin-18 production in peripheral blood mononuclear cells. J Int Med Res 30:144–160PubMed
67.
Zurück zum Zitat DeKruyff R, Fang Y, Umetsu DT (1998) Corticosteroids enhance the capacity of macrophages to induce Th2 cytokine synthesis in CD4+ lymphocytes by inhibiting IL-12 production. J Immunol 160:2231–2237PubMed DeKruyff R, Fang Y, Umetsu DT (1998) Corticosteroids enhance the capacity of macrophages to induce Th2 cytokine synthesis in CD4+ lymphocytes by inhibiting IL-12 production. J Immunol 160:2231–2237PubMed
68.
Zurück zum Zitat Ramirez F, Fowell DJ, Puklavec M, Simmonds S, Mason D (1996) Glucocorticoids promote a Th2 cytokine response by CD4+ T cells in vitro. J Immunol 156:2406–2412PubMed Ramirez F, Fowell DJ, Puklavec M, Simmonds S, Mason D (1996) Glucocorticoids promote a Th2 cytokine response by CD4+ T cells in vitro. J Immunol 156:2406–2412PubMed
69.
Zurück zum Zitat Kashiwada M, Cassel SL, Colgan JD, Rothman PB (2011) NFIL3/E4BP4 controls type 2 T helper cell cytokine expression. EMBO J 30:2071–2082PubMedPubMedCentral Kashiwada M, Cassel SL, Colgan JD, Rothman PB (2011) NFIL3/E4BP4 controls type 2 T helper cell cytokine expression. EMBO J 30:2071–2082PubMedPubMedCentral
70.
Zurück zum Zitat So AYL, Bernal TU, Pillsbury ML, Yamamoto KR, Feldman BJ (2009) Glucocorticoid regulation of the circadian clock modulates glucose homeostasis. Proc Natl Acad Sci U S A 106:17582–17587PubMedPubMedCentral So AYL, Bernal TU, Pillsbury ML, Yamamoto KR, Feldman BJ (2009) Glucocorticoid regulation of the circadian clock modulates glucose homeostasis. Proc Natl Acad Sci U S A 106:17582–17587PubMedPubMedCentral
71.
Zurück zum Zitat Nakayama T, Yamashita M (2008) Initiation and maintenance of Th2 cell identity. Curr Opin Immunol 20:265–271PubMed Nakayama T, Yamashita M (2008) Initiation and maintenance of Th2 cell identity. Curr Opin Immunol 20:265–271PubMed
72.
Zurück zum Zitat Endo Y, Hirahara K, Yagi R, Tumes DJ, Nakayama T (2014) Pathogenic memory type Th2 cells in allergic inflammation. Trends Immunol 35:69–78PubMed Endo Y, Hirahara K, Yagi R, Tumes DJ, Nakayama T (2014) Pathogenic memory type Th2 cells in allergic inflammation. Trends Immunol 35:69–78PubMed
73.
Zurück zum Zitat Yang JF, Sundrud MS, Skepner J, Yamagata T (2014) Targeting Th17 cells in autoimmune diseases. Trends Pharmacol Sci 35:493–500PubMed Yang JF, Sundrud MS, Skepner J, Yamagata T (2014) Targeting Th17 cells in autoimmune diseases. Trends Pharmacol Sci 35:493–500PubMed
74.
Zurück zum Zitat Banuelos J, Cao Y, Shin SC, Lu NZ (2017) Immunopathology alters Th17 cell glucocorticoid sensitivity. Allergy 72:331–341PubMed Banuelos J, Cao Y, Shin SC, Lu NZ (2017) Immunopathology alters Th17 cell glucocorticoid sensitivity. Allergy 72:331–341PubMed
75.
Zurück zum Zitat Hino R, Kabashima R, Kawakami C, Sugita K, Nakamura M, Tokura Y (2011) Circulating Th17 cell fluctuation in psoriatic patients treated with topical calcipotriol and betamethasone butyrate propionate. J Eur Acad Dermatol Venereol 25:243–244 Hino R, Kabashima R, Kawakami C, Sugita K, Nakamura M, Tokura Y (2011) Circulating Th17 cell fluctuation in psoriatic patients treated with topical calcipotriol and betamethasone butyrate propionate. J Eur Acad Dermatol Venereol 25:243–244
76.
Zurück zum Zitat Lovato P, Norsgaard H, Tokura Y, Ropke MA (2017) Calcipotriol and betamethasone dipropionate exert additive inhibitory effects on the cytokine expression of inflammatory dendritic cell-Th17 cell axis in psoriasis. J Dermatol Sci 85:147–147PubMed Lovato P, Norsgaard H, Tokura Y, Ropke MA (2017) Calcipotriol and betamethasone dipropionate exert additive inhibitory effects on the cytokine expression of inflammatory dendritic cell-Th17 cell axis in psoriasis. J Dermatol Sci 85:147–147PubMed
77.
Zurück zum Zitat Prado C, de Paz B, Gomez J, Lopez P, Rodriguez-Carrio J, Suarez A (2011) Glucocorticoids enhance Th17/Th1 imbalance and signal transducer and activator of transcription 3 expression in systemic lupus erythematosus patients. Rheumatology 50:1794–1801PubMed Prado C, de Paz B, Gomez J, Lopez P, Rodriguez-Carrio J, Suarez A (2011) Glucocorticoids enhance Th17/Th1 imbalance and signal transducer and activator of transcription 3 expression in systemic lupus erythematosus patients. Rheumatology 50:1794–1801PubMed
78.
Zurück zum Zitat Ramesh R, Kozhaya L, McKevitt K, Djuretic IM, Carlson TJ, Quintero MA, McCauley JL, Abreu MT, Unutmaz D, Sundrud MS (2014) Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids. J Exp Med 211:89–104PubMedPubMedCentral Ramesh R, Kozhaya L, McKevitt K, Djuretic IM, Carlson TJ, Quintero MA, McCauley JL, Abreu MT, Unutmaz D, Sundrud MS (2014) Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids. J Exp Med 211:89–104PubMedPubMedCentral
79.
Zurück zum Zitat Paugh SW, Bonten EJ, Savic D, Ramsey LB, Thierfelder WE, Gurung P, Malireddi RKS, Actis M, Mayasundari A, Min J (2015) NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells. Nat Genet 47:607–614PubMedPubMedCentral Paugh SW, Bonten EJ, Savic D, Ramsey LB, Thierfelder WE, Gurung P, Malireddi RKS, Actis M, Mayasundari A, Min J (2015) NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells. Nat Genet 47:607–614PubMedPubMedCentral
80.
Zurück zum Zitat Schewitz-Bowers LP, Lait PJP, Copland DA, Chen P, Wu WT, Dhanda AD, Vistica BP, Williams EL, Liu BY, Jawad S, Li Z, Tucker W, Hirani S, Wakabayashi Y, Zhu J, Sen N, Conway-Campbell BL, Gery I, Dick AD, Wei L, Nussenblatt RB, Lee RW (2015) Glucocorticoid-resistant Th17 cells are selectively attenuated by cyclosporine a. Proc Natl Acad Sci U S A 112:4080–4085PubMedPubMedCentral Schewitz-Bowers LP, Lait PJP, Copland DA, Chen P, Wu WT, Dhanda AD, Vistica BP, Williams EL, Liu BY, Jawad S, Li Z, Tucker W, Hirani S, Wakabayashi Y, Zhu J, Sen N, Conway-Campbell BL, Gery I, Dick AD, Wei L, Nussenblatt RB, Lee RW (2015) Glucocorticoid-resistant Th17 cells are selectively attenuated by cyclosporine a. Proc Natl Acad Sci U S A 112:4080–4085PubMedPubMedCentral
81.
Zurück zum Zitat Zhao J, Lloyd CM, Noble A (2013) Th17 responses in chronic allergic airway inflammation abrogate regulatory T-cell-mediated tolerance and contribute to airway remodeling. Mucosal Immunol 6:335–346PubMed Zhao J, Lloyd CM, Noble A (2013) Th17 responses in chronic allergic airway inflammation abrogate regulatory T-cell-mediated tolerance and contribute to airway remodeling. Mucosal Immunol 6:335–346PubMed
82.
Zurück zum Zitat Kroner JD, Steiger J, Fabri M (2018) Glucocorticoids promote intrinsic human Th17 differentiation. J Invest Dermatol 138:S11–S11 Kroner JD, Steiger J, Fabri M (2018) Glucocorticoids promote intrinsic human Th17 differentiation. J Invest Dermatol 138:S11–S11
83.
Zurück zum Zitat Farrell RJ, Kelleher D (2003) Glucocorticoid resistance in inflammatory bowel disease. J Endocrinol 178:339–346PubMed Farrell RJ, Kelleher D (2003) Glucocorticoid resistance in inflammatory bowel disease. J Endocrinol 178:339–346PubMed
84.
Zurück zum Zitat Hirahara K, Mato N, Hagiwara K, Nakayama T (2018) The pathogenicity of IL-33 on steroid-resistant eosinophilic inflammation via the activation of memory-type ST2+CD4+ T cells. J Leukoc Biol 104:895–901PubMed Hirahara K, Mato N, Hagiwara K, Nakayama T (2018) The pathogenicity of IL-33 on steroid-resistant eosinophilic inflammation via the activation of memory-type ST2+CD4+ T cells. J Leukoc Biol 104:895–901PubMed
85.
Zurück zum Zitat Karagiannidis C, Akdis M, Holopainen P, Woolley NJ, Hense G, Ruckert B, Mantel PY, Menz G, Akdis CA, Blaser K, Schmidt-Weber CB (2004) Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma. J Allergy Clin Immunol 114:1425–1433PubMed Karagiannidis C, Akdis M, Holopainen P, Woolley NJ, Hense G, Ruckert B, Mantel PY, Menz G, Akdis CA, Blaser K, Schmidt-Weber CB (2004) Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma. J Allergy Clin Immunol 114:1425–1433PubMed
86.
Zurück zum Zitat Ugor E, Prenek L, Pap R, Berta G, Ernszt D, Najbauer J, Nemeth P, Boldizsar F, Berki T (2018) Glucocorticoid hormone treatment enhances the cytokine production of regulatory T cells by upregulation of Foxp3 expression. Immunobiology 223:422–431PubMed Ugor E, Prenek L, Pap R, Berta G, Ernszt D, Najbauer J, Nemeth P, Boldizsar F, Berki T (2018) Glucocorticoid hormone treatment enhances the cytokine production of regulatory T cells by upregulation of Foxp3 expression. Immunobiology 223:422–431PubMed
87.
Zurück zum Zitat Chen X, Murakami T, Oppenheim JJ, Howard DMZ (2004) Differential response of murine CD4+CD25+ and CD4+CD25− T cells to dexamethasone-induced cell death. Eur J Immunol 34:859–869PubMed Chen X, Murakami T, Oppenheim JJ, Howard DMZ (2004) Differential response of murine CD4+CD25+ and CD4+CD25 T cells to dexamethasone-induced cell death. Eur J Immunol 34:859–869PubMed
88.
Zurück zum Zitat Rocamora-Reverte L, Tuzlak S, von Raffay L, Tisch M, Fiegl H, Drach M, Reichardt HM, Villunger A, Tischner D, Wiegers GJ (2019) Glucocorticoid receptor-deficient Foxp3+ regulatory T cells fail to control experimental inflammatory bowel disease. Front Immunol 10:472PubMedPubMedCentral Rocamora-Reverte L, Tuzlak S, von Raffay L, Tisch M, Fiegl H, Drach M, Reichardt HM, Villunger A, Tischner D, Wiegers GJ (2019) Glucocorticoid receptor-deficient Foxp3+ regulatory T cells fail to control experimental inflammatory bowel disease. Front Immunol 10:472PubMedPubMedCentral
89.
Zurück zum Zitat Tischner D, Gaggl I, Peschel I, Kaufmann M, Tuzlak S, Drach M, Thuille N, Villunger A, Wiegers GJ (2012) Defective cell death signalling along the Bcl-2 regulated apoptosis pathway compromises Treg cell development and limits their functionality in mice. J Autoimmun 38:59–69PubMed Tischner D, Gaggl I, Peschel I, Kaufmann M, Tuzlak S, Drach M, Thuille N, Villunger A, Wiegers GJ (2012) Defective cell death signalling along the Bcl-2 regulated apoptosis pathway compromises Treg cell development and limits their functionality in mice. J Autoimmun 38:59–69PubMed
90.
Zurück zum Zitat Chen X, Oppenheim JJ, Winkler-Pickett RT, Ortaldo JR, Howard OMZ (2006) Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3+CD4+CD25+ T regulatory cells in vivo and enhances their capacity to suppress EAE. Eur J Immunol 36:2139–2149PubMed Chen X, Oppenheim JJ, Winkler-Pickett RT, Ortaldo JR, Howard OMZ (2006) Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3+CD4+CD25+ T regulatory cells in vivo and enhances their capacity to suppress EAE. Eur J Immunol 36:2139–2149PubMed
91.
Zurück zum Zitat Sbiera S, Dexneit T, Reichardt SD, Michel KD, van den Brandt J, Schmull S, Kraus L, Beyer M, Mlynski R, Wortmann S, Allolio B, Reichardt HM, Fassnacht M (2011) Influence of short-term glucocorticoid therapy on regulatory T cells in vivo. PLoS One 6(9):e24345PubMedPubMedCentral Sbiera S, Dexneit T, Reichardt SD, Michel KD, van den Brandt J, Schmull S, Kraus L, Beyer M, Mlynski R, Wortmann S, Allolio B, Reichardt HM, Fassnacht M (2011) Influence of short-term glucocorticoid therapy on regulatory T cells in vivo. PLoS One 6(9):e24345PubMedPubMedCentral
92.
Zurück zum Zitat Stock P, Akbari O, DeKruyff RH, Umetsu DT (2005) Respiratory tolerance is inhibited by the administration of corticosteroids. J Immunol 175:7380–7387PubMed Stock P, Akbari O, DeKruyff RH, Umetsu DT (2005) Respiratory tolerance is inhibited by the administration of corticosteroids. J Immunol 175:7380–7387PubMed
93.
Zurück zum Zitat Wust S, van den Brandt J, Tischner D, Kleiman A, Tuckermann JP, Gold R, Luhder F, Reichardt HM (2008) Peripheral T cells are the therapeutic targets of glucocorticoids in experimental autoimmune encephalomyelitis. J Immunol 180:8434–8443PubMed Wust S, van den Brandt J, Tischner D, Kleiman A, Tuckermann JP, Gold R, Luhder F, Reichardt HM (2008) Peripheral T cells are the therapeutic targets of glucocorticoids in experimental autoimmune encephalomyelitis. J Immunol 180:8434–8443PubMed
94.
Zurück zum Zitat Reiche EMV, Morimoto HK, Nunes SOV (2006) Stress and depression-induced immune dysfunction: implications for the development and progression of cancer. Int Rev Psychiatry 17:515–527 Reiche EMV, Morimoto HK, Nunes SOV (2006) Stress and depression-induced immune dysfunction: implications for the development and progression of cancer. Int Rev Psychiatry 17:515–527
95.
Zurück zum Zitat Bonneau RH, Sheridan JF, Feng N, Glaser R (1991) Stress-induced suppression of herpes simplex virus (HSV)-specific cytotoxic T lymphocyte and natural killer cell activity and enhancement of acute pathogenesis following local HSV infection. Brain Behav Immun 1991(5):170–192 Bonneau RH, Sheridan JF, Feng N, Glaser R (1991) Stress-induced suppression of herpes simplex virus (HSV)-specific cytotoxic T lymphocyte and natural killer cell activity and enhancement of acute pathogenesis following local HSV infection. Brain Behav Immun 1991(5):170–192
96.
Zurück zum Zitat Steelman AJ, Dean DD, Young CR, Smith R, Prentice TW, Meagher MW, Welsh CJR (2009) Restraint stress modulates virus specific adaptive immunity during acute Theiler’s virus infection. Brain Behav Immun 23:830–843PubMedPubMedCentral Steelman AJ, Dean DD, Young CR, Smith R, Prentice TW, Meagher MW, Welsh CJR (2009) Restraint stress modulates virus specific adaptive immunity during acute Theiler’s virus infection. Brain Behav Immun 23:830–843PubMedPubMedCentral
97.
Zurück zum Zitat Elftman MD, Norbury CC, Bonneau RH, Truckenmiller ME (2007) Corticosterone impairs dendritic cell maturation and function. Immunology 122:279–290PubMedPubMedCentral Elftman MD, Norbury CC, Bonneau RH, Truckenmiller ME (2007) Corticosterone impairs dendritic cell maturation and function. Immunology 122:279–290PubMedPubMedCentral
98.
Zurück zum Zitat Elftman MD, Hunzeker JT, Mellinger JC, Bonneau RH, Norbury CC, Truckenmiller ME (2010) Stress-induced glucocorticoids at the earliest stages of herpes simplex virus-1 infection suppress subsequent antiviral immunity, implicating impaired dendritic cell function. J Immunol 184:1867–1875PubMedPubMedCentral Elftman MD, Hunzeker JT, Mellinger JC, Bonneau RH, Norbury CC, Truckenmiller ME (2010) Stress-induced glucocorticoids at the earliest stages of herpes simplex virus-1 infection suppress subsequent antiviral immunity, implicating impaired dendritic cell function. J Immunol 184:1867–1875PubMedPubMedCentral
99.
Zurück zum Zitat Reiche EMV, Nunes SOV, Morimoto HK (2004) Stress, depression, the immune system, and cancer. Lancet Oncol 5:617–625PubMed Reiche EMV, Nunes SOV, Morimoto HK (2004) Stress, depression, the immune system, and cancer. Lancet Oncol 5:617–625PubMed
100.
Zurück zum Zitat De Lorenzo BHP, Brito R, Leal TP, Garcia NP, dos Santos RMM, Alvares-Saraiva AM, Hurtado ECP, dos Reis TCB, Palma BD (2018) Chronic sleep restriction impairs the antitumor immune response in mice. Neuroimmunomodulation 2018(25):59–67 De Lorenzo BHP, Brito R, Leal TP, Garcia NP, dos Santos RMM, Alvares-Saraiva AM, Hurtado ECP, dos Reis TCB, Palma BD (2018) Chronic sleep restriction impairs the antitumor immune response in mice. Neuroimmunomodulation 2018(25):59–67
101.
Zurück zum Zitat Ben-Eliyahu S, Page GG, Yirmiya R, Shakhar G (1999) Evidence that stress and surgical interventions promote tumor development by suppressing natural killer cell activity. Int J Cancer 80:880–888PubMed Ben-Eliyahu S, Page GG, Yirmiya R, Shakhar G (1999) Evidence that stress and surgical interventions promote tumor development by suppressing natural killer cell activity. Int J Cancer 80:880–888PubMed
102.
Zurück zum Zitat Rosenne E, Sorski L, Shaashua L, Neeman E, Matzner P, Levi B, Ben-Eliyahu S (2014) In vivo suppression of NK cell cytotoxicity by stress and surgery: glucocorticoids have a minor role compared to catecholamines and prostaglandins. Brain Behav Immun 37:207–219PubMed Rosenne E, Sorski L, Shaashua L, Neeman E, Matzner P, Levi B, Ben-Eliyahu S (2014) In vivo suppression of NK cell cytotoxicity by stress and surgery: glucocorticoids have a minor role compared to catecholamines and prostaglandins. Brain Behav Immun 37:207–219PubMed
103.
Zurück zum Zitat Dhabhar FS (2009) Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Neuroimmunomodulation 16:300–317PubMedPubMedCentral Dhabhar FS (2009) Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Neuroimmunomodulation 16:300–317PubMedPubMedCentral
104.
Zurück zum Zitat Busillo JM, Azzam KM, Cidlowski JA (2011) Glucocorticoids sensitize the innate immune system through regulation of the NLRP3 inflammasome. J Biol Chem 286:38703–38713PubMedPubMedCentral Busillo JM, Azzam KM, Cidlowski JA (2011) Glucocorticoids sensitize the innate immune system through regulation of the NLRP3 inflammasome. J Biol Chem 286:38703–38713PubMedPubMedCentral
105.
Zurück zum Zitat Wiegers GJ, Reul J (1998) Induction of cytokine receptors by glucocorticoids: functional and pathological significance. Trends Pharmacol Sci 19:317–321PubMed Wiegers GJ, Reul J (1998) Induction of cytokine receptors by glucocorticoids: functional and pathological significance. Trends Pharmacol Sci 19:317–321PubMed
106.
Zurück zum Zitat Sekiyama A, Ueda H, Kashiwamura S, Nishida K, Kawai K, Teshima-kondo S, Rokutan K, Okamura H (2005) IL-18; a cytokine translates a stress into medical science. J Med Investig 52(Suppl):236–239 Sekiyama A, Ueda H, Kashiwamura S, Nishida K, Kawai K, Teshima-kondo S, Rokutan K, Okamura H (2005) IL-18; a cytokine translates a stress into medical science. J Med Investig 52(Suppl):236–239
107.
Zurück zum Zitat Qiu BS, Vallance BA, Blennerhassett PA, Collins SM (1999) The role of CD4+ lymphocytes in the susceptibility of mice to stress-induced reactivation of experimental colitis. Nat Med 5:1178–1182PubMed Qiu BS, Vallance BA, Blennerhassett PA, Collins SM (1999) The role of CD4+ lymphocytes in the susceptibility of mice to stress-induced reactivation of experimental colitis. Nat Med 5:1178–1182PubMed
108.
Zurück zum Zitat Marchetti B, Morale MC, Testa N, Tirolo C, Caniglia S, Amor S, Dijkstra CD, Barden N (2001) Stress, the immune system and vulnerability to degenerative disorders of the central nervous system in transgenic mice expressing glucocorticoid receptor antisense RNA. Brain Res Rev 37:259–272PubMed Marchetti B, Morale MC, Testa N, Tirolo C, Caniglia S, Amor S, Dijkstra CD, Barden N (2001) Stress, the immune system and vulnerability to degenerative disorders of the central nervous system in transgenic mice expressing glucocorticoid receptor antisense RNA. Brain Res Rev 37:259–272PubMed
109.
Zurück zum Zitat Arima Y, Ohki T, Nishikawa N, Higuchi K, Ota M, Tanaka Y, Nio-Kobayashi J, Elfeky M, Sakai R, Mori Y, Kawamoto T, Stofkova A, Sakashita Y, Morimoto Y, Kuwatani M, Iwanaga Y, Yoshioka Y, Sakamoto N, Yoshimura A, Takiguchi M, Sakoda S, Prinz M, Kamimura D, Murakami M (2017) Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit. eLife 6:e25517PubMedPubMedCentral Arima Y, Ohki T, Nishikawa N, Higuchi K, Ota M, Tanaka Y, Nio-Kobayashi J, Elfeky M, Sakai R, Mori Y, Kawamoto T, Stofkova A, Sakashita Y, Morimoto Y, Kuwatani M, Iwanaga Y, Yoshioka Y, Sakamoto N, Yoshimura A, Takiguchi M, Sakoda S, Prinz M, Kamimura D, Murakami M (2017) Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit. eLife 6:e25517PubMedPubMedCentral
110.
Zurück zum Zitat Ogura H, Murakami M, Okuyama Y, Tsuruoka M, Kitabayashi C, Kanamoto M, Nishihara M, Iwakura Y, Hirano T (2008) Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction. Immunity 29:628–636PubMed Ogura H, Murakami M, Okuyama Y, Tsuruoka M, Kitabayashi C, Kanamoto M, Nishihara M, Iwakura Y, Hirano T (2008) Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction. Immunity 29:628–636PubMed
111.
Zurück zum Zitat Rosenberger PH, Ickovics JR, Epel E, Nadler E, Jokl P, Fulkerson JP, Tillie JM, Dhabhar FS (2009) Surgical stress-induced immune cell redistribution profiles predict short-term and long-term postsurgical recovery. J Bone Joint Surg Am 91A:2783–2794 Rosenberger PH, Ickovics JR, Epel E, Nadler E, Jokl P, Fulkerson JP, Tillie JM, Dhabhar FS (2009) Surgical stress-induced immune cell redistribution profiles predict short-term and long-term postsurgical recovery. J Bone Joint Surg Am 91A:2783–2794
112.
Zurück zum Zitat Dhabhar FS, Satoskar AR, Bluethmann H, David JR, McEwen BS (2000) Stress-induced enhancement of skin immune function: a role for γ interferon. Proc Natl Acad Sci U S A 97:2846–2851PubMedPubMedCentral Dhabhar FS, Satoskar AR, Bluethmann H, David JR, McEwen BS (2000) Stress-induced enhancement of skin immune function: a role for γ interferon. Proc Natl Acad Sci U S A 97:2846–2851PubMedPubMedCentral
113.
Zurück zum Zitat Dhabhar FS, Miller AH, McEwen BS, Spencer RL (1995) Effects of stress on immune cell distribution. Dynamics and hormonal mechanisms. J Immunol 154:5511–5527PubMed Dhabhar FS, Miller AH, McEwen BS, Spencer RL (1995) Effects of stress on immune cell distribution. Dynamics and hormonal mechanisms. J Immunol 154:5511–5527PubMed
114.
Zurück zum Zitat Miller AH, Spencer RL, Hassett J, Kim C, Rhee R, Ciurea D, Dhabhar F, McEwen B, Stein M (1994) Effects of selective type-I and type-II adrenal-steroid agonists on immune cell distribution. Endocrinology 135:1934–1944PubMed Miller AH, Spencer RL, Hassett J, Kim C, Rhee R, Ciurea D, Dhabhar F, McEwen B, Stein M (1994) Effects of selective type-I and type-II adrenal-steroid agonists on immune cell distribution. Endocrinology 135:1934–1944PubMed
115.
Zurück zum Zitat Dhabhar FS, McEwen BS (1999) Enhancing versus suppressive effects of stress hormones on skin immune function. Proc Natl Acad Sci U S A 96:1059–1064PubMedPubMedCentral Dhabhar FS, McEwen BS (1999) Enhancing versus suppressive effects of stress hormones on skin immune function. Proc Natl Acad Sci U S A 96:1059–1064PubMedPubMedCentral
Metadaten
Titel
Control of immunity by glucocorticoids in health and disease
verfasst von
Akihiro Shimba
Koichi Ikuta
Publikationsdatum
20.11.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Seminars in Immunopathology / Ausgabe 6/2020
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-020-00827-8

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