Minireview: Glucocorticoids in autoimmunity: Unexpected targets and mechanisms

Molecular Endocrinology

Volumn 25, Issue 7, 2011, Pages 1075-1086

  Flammer, Jamie R ^a   Rogatsky, Inez ^a  

^a HOSPITAL FOR SPECIAL SURGERY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA INTERFERON; CYTOKINE; GLUCOCORTICOID; INTERFERON; TRANSCRIPTION FACTOR;

ANEMIA; ANTIINFLAMMATORY ACTIVITY; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CHRONIC MYELOID LEUKEMIA; CUTANEOUS T CELL LYMPHOMA; CYTOKINE PRODUCTION; HELPER CELL; HUMAN; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; MEDICAL LITERATURE; NONHUMAN; POLARIZATION; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE; THROMBOCYTOPENIA; VIRUS HEPATITIS;

ANIMALS; AUTOIMMUNITY; GLUCOCORTICOIDS; HUMANS; INTERFERON TYPE I; LYMPHOCYTE ACTIVATION; RECEPTORS, GLUCOCORTICOID; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS; T-LYMPHOCYTES, HELPER-INDUCER;

EID: 79959851491     PISSN: 08888809     EISSN: None     Source Type: Journal    
DOI: 10.1210/me.2011-0068     Document Type: Review

References (129)

1. Ward E, Slocumb CH, Polley HF, Kendall EC, Hench PS 1951 Clinical effects of cortisone administered orally to 100 patients with rheumatoid arthritis. Ann Rheum Dis 10:477-484
2. Hench PS, Kendall EC, Slocumb CH, Polley HF 1949 Adrenocortical hormone in arthritis: preliminary report. Ann Rheum Dis 8:97-104
3. Schappert SM, Rechtsteiner EA 2008 Ambulatory medical care utilization estimates for 2006. Natl Health Stat Report:1-29
4. Tarcic N, Ovadia H, Weiss DW, Weidenfeld J 1998 Restraint stress-induced thymic involution and cell apoptosis are dependent on endogenous glucocorticoids. J Neuroimmunol 82:40-46
5. Pratt WB, Galigniana MD, Harrell JM, DeFranco DB 2004 Role of hsp90 and the hsp90-binding immunophilins in signalling protein movement. Cell Signal 16:857-872
6. Lefstin JA, Yamamoto KR 1998 Allosteric effects of DNA on transcriptional regulators. Nature 392:885-888
7. Margolis RN, Evans RM, O'Malley BW 2005 The nuclear receptor signaling atlas: development of a functional atlas of nuclear receptors. Mol Endocrinol 19:2433-2436
8. Stallcup MR, Kim JH, Teyssier C, Lee YH, Ma H, Chen D 2003 The roles of protein-protein interactions and protein methylation in transcriptional activation by nuclear receptors and their coactivators. J Steroid Biochem Mol Biol 85:139-145
9. Xu J, Li Q 2003 Review of the in vivo functions of the p160 steroid receptor coactivator family. Mol Endocrinol 17:1681-1692
10. Rogatsky I, Luecke HF, Leitman DC, Yamamoto KR 2002 Alternate surfaces of transcriptional coregulator GRIP1 function in different glucocorticoid receptor activation and repression contexts. Proc Natl Acad Sci USA 99:16701-16706
11. Rogatsky I, Zarember KA, Yamamoto KR 2001 Factor recruitment and TIF2/GRIP1 corepressor activity at a collagenase-3 response element that mediates regulation by phorbol esters and hormones. EMBO J 20:6071-6083
12. Tveita AA 2010 The danger model in deciphering autoimmunity. Rheumatology 49:632-639
13. Sundrud MS, Nolan MA 2010 Synergistic and combinatorial control of T cell activation and differentiation by transcription factors. Curr Opin Immunol 22:286-292
14. Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM 1993 Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 260:547-549
15. Rogge L, D'Ambrosio D, Biffi M, Penna G, Minetti LJ, Presky DH, Adorini L, Sinigaglia F 1998 The role of Stat4 in species-specific regulation of Th cell development by type I IFNs. J Immunol 161:6567-6574
16. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT 2005 Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123-1132
17. Manel N, Unutmaz D, Littman DR 2008 The differentiation of human T(H)-17 cells requires transforming growth factor-β and induction of the nuclear receptor RORγt. Nat Immunol 9:641-649
18. Damsker JM, Hansen AM, Caspi RR 2010 Th1 and Th17 cells: adversaries and collaborators. Ann NY Acad Sci 1183:211-221
19. Terato K, Hasty KA, Reife RA, Cremer MA, Kang AH, Stuart JM 1992 Induction of arthritis with monoclonal antibodies to collagen. J Immunol 148:2103-2108
20. Steinman L 2007 A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat Med 13:139-145
21. Takahashi S, Fossati L, Iwamoto M, Merino R, Motta R, Kobayakawa T, Izui S 1996 Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice. J Clin Invest 97:1597-1604
22. Wang B, Andé I, Gonzalez A, Katz JD, Aguet M, Benoist C, Mathis D 1997 Interferon-_ impacts at multiple points during the progression of autoimmune diabetes. Proc Natl Acad Sci USA 94:13844-13849
23. Hölttä V, Klemetti P, Sipponen T, Westerholm-Ormio M, Kociubinski G, Salo H, Räsänen L, Kolho KL, Färkkilä M, Savilahti E, Vaarala O 2008 IL-23/IL-17 immunity as a hallmark of Crohn's disease. Inflamm Bowel Dis 14:1175-1184
24. Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, Ouyang W 2007 Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445:648-651
25. Matusevicius D, Kiviskk P, He B, Kostulas N, Ozenci V, Fredrikson S, Link H 1999 Interleukin-17mRNAexpression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult Scler 5:101-104
26. Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L, Miossec P 1999 Human interleukin-17: a T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum 42:963-970
27. Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, Fugger L 2008 Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 172:146-155
28. Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, Giuliani F, Arbour N, Becher B, Prat A 2007 Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 13:1173-1175
29. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ 2005 IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233-240
30. Chen Y, Langrish CL, McKenzie B, Joyce-Shaikh B, Stumhofer JS, McClanahan T, Blumenschein W, Churakovsa T, Low J, Presta L, Hunter CA, Kastelein RA, Cua DJ 2006 Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J Clin Invest 116:1317-1326
31. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C 2005 A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6:1133-1141
32. Edgerton C, Crispín JC, Moratz CM, Bettelli E, Oukka M, Simovic M, Zacharia A, Egan R, Chen J, Dalle Lucca JJ, Juang YT, Tsokos GC 2009 IL-17 producing CD4+ T cells mediate accelerated ischemia/reperfusion-induced injury in autoimmunity-prone mice. Clin Immunol 130:313-321
33. Crispín JC, Oukka M, Bayliss G, Cohen RA, Van Beek CA, Stillman IE, Kyttaris VC, Juang YT, Tsokos GC 2008 Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J Immunol 181:8761-8766
34. Wong CK, Lit LC, Tam LS, Li EK, Wong PT, Lam CW 2008 Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol 127:385-393
35. Luger D, Silver PB, Tang J, Cua D, Chen Z, Iwakura Y, Bowman EP, Sgambellone NM, Chan CC, Caspi RR 2008 Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J Exp Med 205:799-810
36. Elenkov IJ 2004 Glucocorticoids and the Th1/Th2 balance. Ann NY Acad Sci 1024:138-146
37. Ramírez F, Fowell DJ, Puklavec M, Simmonds S, Mason D 1996 Glucocorticoids promote a TH2 cytokine response by CD4+ T cells in vitro. J Immunol 156:2406-2412
38. DeKruyff RH, 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 160:2231-2237
39. 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 158:5589-5595
40. Wu CY, Wang K, McDyer JF, Seder RA 1998 Prostaglandin E2 and dexamethasone inhibit IL-12 receptor expression and IL-12 responsiveness. J Immunol 161:2723-2730
41. Fahey AJ, Robins RA, Kindle KB, Heery DM, Constantinescu CS 2006 Effects of glucocorticoids on STAT4 activation in human T cells are stimulus-dependent. J Leukoc Biol 80:133-144
42. Luther C, Adamopoulou E, Stoeckle C, Brucklacher-Waldert V, Rosenkranz D, Stoltze L, Lauer S, Poeschel S, Melms A, Tolosa E 2009 Prednisolone treatment induces tolerogenic dendritic cells and a regulatory milieu in myasthenia gravis patients. J Immunol 183:841-848
43. Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, Levy DE, Leonard WJ, Littman DR 2007 IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8:967-974
44. Waage A, Slupphaug G, Shalaby R 1990 Glucocorticoids inhibit the production of IL6 from monocytes, endothelial cells and fibroblasts. Eur J Immunol 20:2439-2443
45. Flammer JR, Dobrovolna J, Kennedy MA, Chinenov Y, Glass CK, Ivashkiv LB, Rogatsky I 2010 Type I interferon signaling pathway is a target for glucocorticoid Inhibition. Mol Cell Biol 30:4564-4574
46. Zitnik RJ, Whiting NL, Elias JA 1994 Glucocorticoid inhibition of interleukin-1-induced interleukin-6 production by human lung fibroblasts: evidence for transcriptional and post-transcriptional regulatory ńmechanisms. Am J Respir Cell Mol Biol 10:643-650
47. Vieira PL, Kaliski P, Wierenga EA, Kapsenberg ML, de Jong EC 1998 Glucocorticoids inhibit bioactive IL-12p70 production by in vitro-generated human dendritic cells without affecting their T cell stimulatory potential. J Immunol 161:5245-5251
48. Monari C, Bevilacqua S, Piccioni M, Pericolini E, Perito S, Calvitti M, Bistoni F, Kozel TR, Vecchiarelli A 2009 A microbial polysaccharide reduces the severity of rheumatoid arthritis by influencing Th17 differentiation and proinflammatory cytokines production. J Immunol 183:191-200
49. Momcilović M, Miljković Z, Popadić D, Marković M, Savić E, Ramić Z, Miljković D, Mostarica-Stojković M 2008 Methylprednisolone inhibits interleukin-17 and interferon-γ expression by both naive and primed T cells. BMC Immunol 9:47
50. Yang K, Wen J, Liu X, Kijlstra A, Chen L, Chi W, Zhou H, Huang X, Yang P 2009 Inhibitory effect of rapamycin and dexamethasone on production of IL-17 and IFN-γ in Vogt-Koyanagi-Harada patients. Br J Ophthalmol 93:249-253
51. Velten FW, Duperrier K, Bohlender J, Metharom P, Goerdt S 2004 A gene signature of inhibitory MHC receptors identifies a BDCA3(+) subset of IL-10-induced dendritic cells with reduced allostimulatory capacity in vitro. Eur J Immunol 34:2800-2811
52. Duperrier K, Velten FW, Bohlender J, Demory A, Metharom P, Goerdt S 2005 Immunosuppressive agents mediate reduced allostimulatory properties of myeloid-derived dendritic cells despite induction of divergent molecular phenotypes. Mol Immunol 42: 1531-1540
53. Bornstein SR, Zacharowski P, Schumann RR, Barthel A, Tran N, Papewalis C, Rettori V, McCann SM, Schulze-Osthoff K, Scherbaum WA, Tarnow J, Zacharowski K 2004 Impaired adrenal stress response in toll-like receptor 2-deficient mice. Proc Natl Acad Sci USA 101:16695-16700
54. Graudal N, Jürgens G 2010 Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisons. Arthritis Rheum 62:2852-2863
55. Gorter SL, Bijlsma JW, Cutolo M, Gomez-Reino J, Kouloumas M, Smolen JS, Landewé R 2010 Current evidence for the management of rheumatoid arthritis with glucocorticoids: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 69:1010-1014
56. De Bosscher K, Haegeman G 2009 Minireview: latest perspectives on antiinflammatory actions of glucocorticoids. Mol Endocrinol 23:281-291
57. Jonat C, Rahmsdorf HJ, Park KK, Cato AC, Gebel S, Ponta H, Herrlich P 1990 Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell 62:1189-1204
58. Yang-Yen HF, Chambard JC, Sun YL, Smeal T, Schmidt TJ, Drouin J, Karin M 1990 Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell 62:1205-1215
59. Nissen RM, Yamamoto KR 2000 The glucocorticoid receptor inhibits NF_B by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev 14: 2314-2329
60. Luecke HF, Yamamoto KR 2005 The glucocorticoid receptor blocks P-TEFb recruitment by NF_B to effect promoter-specific transcriptional repression. Genes Dev 19:1116-1127
61. König H, Ponta H, Rahmsdorf HJ, Herrlich P 1992 Interference between pathway-specific transcription factors: glucocorticoids antagonize phorbol ester-induced AP-1 activity without altering AP-1 site occupation in vivo. EMBO J 11:2241-2246
62. Yamamoto KR, Darimont BD, Wagner RL, Iñiguez-Lluhí JA 1998 Building transcriptional regulatory complexes: signals and surfaces. Cold Spring Harb Symp Quant Biol 63:587-598
63. Ray A, Prefontaine KE 1994 Physical association and functional antagonism between the p65 subunit of transcription factor NF-κB and the glucocorticoid receptor. Proc Natl Acad Sci USA 91:752-756
64. Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, Lin SC, Heyman RA, Rose DW, Glass CK, Rosenfeld MG 1996 A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 85:403-414
65. De Bosscher K, Vanden Berghe W, Haegeman G 2001 Glucocorticoid repression of AP-1 is not mediated by competition for nuclear coactivators. Mol Endocrinol 15:219-227
66. De Bosscher K, Vanden Berghe W, Vermeulen L, Plaisance S, Boone E, Haegeman G 2000 Glucocorticoids repress NF-κBdriven genes by disturbing the interaction of p65 with the basal transcription machinery, irrespective of coactivator levels in the cell. Proc Natl Acad Sci USA 97:3919-3924
67. Scheinman RI, Cogswell PC, Lofquist AK, Baldwin Jr AS 1995 Role of transcriptional activation of I κ B α in mediation of immunosuppression by glucocorticoids. Science 270:283-286
68. Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin M 1995 Immunosuppression by glucocorticoids: inhibition of NF-κB activity through induction of I κB synthesis. Science 270:286-290
69. Brostjan C, Anrather J, Csizmadia V, Stroka D, Soares M, Bach FH, Winkler H 1996 Glucocorticoid-mediated repression of NFκB activity in endothelial cells does not involve induction of IκBα synthesis. J Biol Chem 271:19612-19616
70. Pérez P, Page A, Bravo A, Del Río M, Giménez-Conti I, Budunova I, Slaga TJ, Jorcano JL 2001 Altered skin development and impaired proliferative and inflammatory responses in transgenic mice overexpressing the glucocorticoid receptor. FASEB J 15: 2030-2032
71. De Bosscher K, Schmitz ML, Vanden Berghe W, Plaisance S, Fiers W, Haegeman G 1997 Glucocorticoid-mediated repression of nuclear factor-_B-dependent transcription involves direct interference with transactivation. Proc Natl Acad Sci USA 94:13504-13509
72. Cato A, Schaecke H, Asadullah K 2002 Recent advances in glucocorticoid receptor action. Berlin: Springer
73. Kassel O, Sancono A, Krätzschmar J, Kreft B, Stassen M, Cato AC 2001 Glucocorticoids inhibitMAPkinase via increased expression and decreased degradation of MKP-1. EMBO J 20:7108-7116
74. Lasa M, Abraham SM, Boucheron C, Saklatvala J, Clark AR 2002 Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38. Mol Cell Biol 22:7802-7811
75. 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 203:1883-1889
76. Mittelstadt PR, Ashwell JD 2001 Inhibition of AP-1 by the glucocorticoid- inducible protein GILZ. J Biol Chem 276:29603-29610
77. Ayroldi E, Migliorati G, Bruscoli S, Marchetti C, Zollo O, Cannarile L, D'Adamio F, Riccardi C 2001 Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor κB. Blood 98:743-753
78. Ank N, West H, Paludan SR 2006 IFN-λ: novel antiviral cytokines. J Interferon Cytokine Res 26:373-379
79. Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM 2003 IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 4:63-68
80. Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, Langer JA, Sheikh F, Dickensheets H, Donnelly RP 2003 IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 4:69-77
81. Evans AS, Rothfield NF, Niederman JC 1971 Raised antibody titres to E.B. virus in systemic lupus erythematosus. Lancet 1:167-168
82. James JA, Kaufman KM, Farris AD, Taylor-Albert E, Lehman TJ, Harley JB 1997 An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus. J Clin Invest 100:3019-3026
83. Rönnblom LE, Alm GV, Oberg KE 1990 Possible induction of systemic lupus erythematosus by interferon-α treatment in a patient with a malignant carcinoid tumour. J Intern Med 227:207-210
84. Wesche B, Jaeckel E, Trautwein C, Wedemeyer H, Falorni A, Frank H, von zur Mühlen A, Manns MP, Brabant G 2001 Induction of autoantibodies to the adrenal cortex and pancreatic islet cells by interferon α therapy for chronic hepatitis C. Gut 48:378- 383
85. Kiehne K, Kloehn S, Hinrichsen H, Gallwitz B, Mönig H 1997 Thyroid autoantibodies and thyroid dysfunction during treatment with interferon-α for chronic hepatitis C. Endocrine 6:231-234
86. Rosenthal GJ, Stranahan 3rd RP, Thompson M, Blair P, Germolec DR, Comment CE, Schwab K, Luster MI 1990 Organ-specific hematopoietic changes induced by a recombinant human interferon- _ in mice. Fundam Appl Toxicol 14:666-675
87. Rahman A, Isenberg DA 2008 Systemic lupus erythematosus. N Engl J Med 358:929-939
88. Hargraves MM 1969 Discovery of the LE cell and its morphology. Mayo Clin Proc 44:579-599
89. Friou GJ 1967 Antinuclear antibodies: diagnostic significance and methods. Arthritis Rheum 10:151-159
90. Preble OT, Black RJ, Friedman RM, Klippel JH, Vilcek J 1982 Systemic lupus erythematosus: presence in human serum of an unusual acid-labile leukocyte interferon. Science 216:429-431
91. Hooks JJ, Moutsopoulos HM, Geis SA, Stahl NI, Decker JL, Notkins AL 1979 Immune interferon in the circulation of patients with autoimmune disease. N Engl J Med 301:5-8
92. Bengtsson AA, Sturfelt G, Truedsson L, Blomberg J, Alm G, Vallin H, Rönnblom L 2000 Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. Lupus 9:664-671
93. Ytterberg SR, Schnitzer TJ 1982 Serum interferon levels in patients with systemic lupus erythematosus. Arthritis Rheum 25: 401-406
94. von Wussow P, Jakschies D, Hochkeppel H, Horisberger M, Hartung K, Deicher H 1989 MXhomologous protein in mononuclear cells from patients with systemic lupus erythematosus. Arthritis Rheum 32:914-918
95. Crow MK, Wohlgemuth J 2003 Microarray analysis of gene expression in lupus. Arthritis Res Ther 5:279-287
96. Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J, Pascual V 2003 Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med 197:711-723
97. Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, Shark KB, Grande WJ, Hughes KM, Kapur V, Gregersen PK, Behrens TW 2003 Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci USA 100:2610-2615
98. Levy DE, Marié I, Prakash A 2003 Ringing the interferon alarm: differential regulation of gene expression at the interface between innate and adaptive immunity. Curr Opin Immunol 15:52-58
99. Marié I, Durbin JE, Levy DE 1998 Differential viral induction of distinct interferon-_ genes by positive feedback through interferon regulatory factor-7. EMBO J 17:6660-6669
100. Thanos D, Maniatis T 1995 Identification of the rel family members required for virus induction of the human β interferon gene. Mol Cell Biol 15:152-164
101. Sharma S, tenOever BR, Grandvaux N, Zhou GP, Lin R, Hiscott J 2003 Triggering the interferon antiviral response through an IKK-related pathway. Science 300:1148-1151
102. Geiss G, Jin G, Guo J, Bumgarner R, Katze MG, Sen GC 2001 A comprehensive view of regulation of gene expression by doublestranded RNA-mediated cell signaling. J Biol Chem 276:30178-30182
103. Shuai K, Liu B 2003 Regulation of JAK-STAT signalling in the immune system. Nat Rev Immunol 3:900-911
104. Martinez-Moczygemba M, Gutch MJ, French DL, Reich NC 1997 Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-α-stimulated transcription factor ISGF3. J Biol Chem 272:20070-20076
105. McCoy CE, Carpenter S, Pålsson-McDermott EM, Gearing LJ, O'Neill LA 2008 Glucocorticoids inhibit IRF3 phosphorylation in response to Toll-like receptor-3 and -4 by targeting TBK1 activation. J Biol Chem 283:14277-14285
106. Kishore N, Huynh QK, Mathialagan S, Hall T, Rouw S, Creely D, Lange G, Caroll J, Reitz B, Donnelly A, Boddupalli H, Combs RG, Kretzmer K, Tripp CS 2002 IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2. J Biol Chem 277:13840-13847
107. Hemmi H, Takeuchi O, Sato S, Yamamoto M, Kaisho T, Sanjo H, Kawai T, Hoshino K, Takeda K, Akira S 2004 The roles of two IκB kinase-related kinases in lipopolysaccharide and double strandedRNAsignaling and viral infection. J Exp Med 199:1641-1650
108. Reily MM, Pantoja C, Hu X, Chinenov Y, Rogatsky I 2006 The GRIP1:IRF3 interaction as a target for glucocorticoid receptormediated immunosuppression. EMBO J 25:108-117
109. Ogawa S, Lozach J, Benner C, Pascual G, Tangirala RK, Westin S, Hoffmann A, Subramaniam S, David M, Rosenfeld MG, Glass CK 2005 Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell 122:707-721
110. Guiducci C, Gong M, Xu Z, Gill M, Chaussabel D, Meeker T, Chan JH, Wright T, Punaro M, Bolland S, Soumelis V, Banchereau J, Coffman RL, Pascual V, Barrat FJ 2010 TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus. Nature 465:937-941
111. Lepelletier Y, Zollinger R, Ghirelli C, Raynaud F, Hadj-Slimane R, Cappuccio A, Hermine O, Liu YJ, Soumelis V 2010 Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid predendritic cells (pDCs). Blood 116:3389-3397
112. Bianchi M, Meng C, Ivashkiv LB 2000 Inhibition of IL-2-induced Jak-STAT signaling by glucocorticoids. Proc Natl Acad Sci USA 97:9573-9578
113. Stöcklin E, Wissler M, Gouilleux F, Groner B 1996 Functional interactions between Stat5 and the glucocorticoid receptor. Nature 383:726-728
114. Lerner L, Henriksen MA, Zhang X, Darnell Jr JE 2003 STAT3- dependent enhanceosome assembly and disassembly: synergy with GR for full transcriptional increase of the _ 2-macroglobulin gene. Genes Dev 17:2564-2577
115. Lechner J, Welte T, Tomasi JK, Bruno P, Cairns C, Gustafsson J, Doppler W 1997 Promoter-dependent synergy between glucocorticoid receptor and Stat5 in the activation of _-casein gene transcription. J Biol Chem 272:20954-20960
116. Cella N, Groner B, Hynes NE 1998 Characterization of Stat5a and Stat5b homodimers and heterodimers and their association with the glucocortiocoid receptor in mammary cells. Mol Cell Biol 18:1783-1792
117. Jeong JW, Kwak I, Lee KY, White LD, Wang XP, Brunicardi FC, O'Malley BW, DeMayo FJ 2006 The genomic analysis of the impact of steroid receptor coactivators ablation on hepatic metabolism. Mol Endocrinol 20:1138-1152
118. Chopra AR, Louet JF, Saha P, An J, Demayo F, Xu J, York B, Karpen S, Finegold M, Moore D, Chan L, Newgard CB, O'Malley BW 2008 Absence of the SRC-2 coactivator results in a glycogenopathy resembling Von Gierke's disease. Science 322:1395-1399
119. Bhandare R, Damera G, Banerjee A, Flammer JR, Keslacy S, Rogatsky I, Panettieri RA, Amrani Y, Tliba O 2010 Glucocorticoid receptor interacting protein-1 restores glucocorticoid responsiveness in steroid-resistant airway structural cells. Am J Respir Cell Mol Biol 42:9-15
120. Gehin M, Mark M, Dennefeld C, Dierich A, Gronemeyer H, Chambon P 2002 The function of TIF2/GRIP1 in mouse reproduction is distinct from those of SRC-1 and p/CIP. Mol Cell Biol 22:5923-5937
121. Picard F, Géhin M, Annicotte J, Rocchi S, Champy MF, O'Malley BW, Chambon P, Auwerx J 2002 SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell 111:931- 941
122. Mukherjee A, Soyal SM, Fernandez-Valdivia R, Gehin M, Chambon P, Demayo FJ, Lydon JP, O'Malley BW 2006 Steroid receptor coactivator 2 is critical for progesterone-dependent uterine function and mammary morphogenesis in the mouse. Mol Cell Biol 26:6571-6583
123. Patchev AV, Fischer D, Wolf SS, Herkenham M, Götz F, Gehin M, Chambon P, Patchev VK, Almeida OF 2007 Insidious adrenocortical insufficiency underlies neuroendocrine dysregulation in TIF-2 deficient mice. FASEB J 21:231-238
124. Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge RM, Bauer JW, Ortmann WA, Koeuth T, Gonzá lez Escribano MF, Pons-Estel B, Petri M, Daly M, Gregersen PK, Martín J, Altshuler D, Behrens TW, Alarcó n-Riquelme ME 2006 A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 38:550-555
125. Sigurdsson S, Nordmark G, Göring HH, Lindroos K, Wiman AC, Sturfelt G, Jönsen A, Rantapää-Dahlqvist S, Möller B, Kere J, Koskenmies S, Widén E, Eloranta ML, Julkunen H, Kristjansdottir H, Steinsson K, Alm G, Rönnblom L, Syvänen AC 2005 Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus. Am J Hum Genet 76:528-537
126. Fanzo JC, Yang W, Jang SY, Gupta S, Chen Q, Siddiq A, Greenberg S, Pernis AB 2006 Loss of IRF-4-binding protein leads to the spontaneous development of systemic autoimmunity. J Clin Invest 116:703-714
127. Biswas PS, Bhagat G, Pernis AB 2010 IRF4 and its regulators: evolving insights into the pathogenesis of inflammatory arthritis? Immunol Rev 233:79-96
128. Chen Q, Yang W, Gupta S, Biswas P, Smith P, Bhagat G, Pernis AB 2008 IRF-4-binding protein inhibits interleukin-17 and interleukin- 21 production by controlling the activity of IRF-4 transcription factor. Immunity 29:899-911
129. Biswas PS, Gupta S, Chang E, Song L, Stirzaker RA, Liao JK, Bhagat G, Pernis AB 2010 Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and the development of autoimmunity in mice. J Clin Invest 120:3280-3295