RORγt inhibitors suppress TH17 responses in inflammatory arthritis and inflammatory bowel disease

Journal of Allergy and Clinical Immunology

Volumn 137, Issue 3, 2016, Pages 960-963

  De Wit, Jelle ^a   Al Mossawi, M Hussein ^a   Hühn, Michael H ^b   Arancibia Cárcamo, Carolina V ^b   Doig, Karen ^a   Kendrick, Benjamin ^a   Gundle, Roger ^a   Taylor, Peter ^c   McClanahan, Terri ^d   Murphy, Erin ^d   Zhang, Hongjun ^d   Barr, Ken ^d   Miller, J Richard ^d   Hu, Xiao ^d   Aicher, Thomas D ^e   Morgan, Rodney W ^e   Glick, Gary D ^f   Zaller, Dennis ^d   Correll, Craig ^d   Powrie, Fiona ^b,g   Bowness, Paul ^a,c   more..

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d MERCK RESEARCH LABORATORIES   (United States)

^e Lycera Corporation   (United States)

^f UNIVERSITY OF MICHIGAN   (United States)

^g UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DIGOXIN; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 17; INTERLEUKIN 17F; INTERLEUKIN 22; INTERLEUKIN 26; RETINOIC ACID RECEPTOR; STEROID RECEPTOR COACTIVATOR 1; INDAZOLE DERIVATIVE; MRL-248; MRL-367; RETINOID RELATED ORPHAN RECEPTOR GAMMA;

CELL PROLIFERATION; FLOW CYTOMETRY; FLUORESCENCE RESONANCE ENERGY TRANSFER; GENOME-WIDE ASSOCIATION STUDY; HELPER CELL; HUMAN; IC50; IMMUNE RESPONSE; INFLAMMATORY BOWEL DISEASE; LETTER; MONONUCLEAR CELL; PRIORITY JOURNAL; RHEUMATOID ARTHRITIS; SYNOVIUM; ANTAGONISTS AND INHIBITORS; ARTHRITIS; BIOSYNTHESIS; CHEMISTRY; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; INFLAMMATORY BOWEL DISEASES; METABOLISM; T LYMPHOCYTE SUBPOPULATION; TH17 CELL;

ARTHRITIS; GENE EXPRESSION REGULATION; HUMANS; INDAZOLES; INFLAMMATORY BOWEL DISEASES; INTERLEUKIN-17; NUCLEAR RECEPTOR SUBFAMILY 1, GROUP F, MEMBER 3; T-LYMPHOCYTE SUBSETS; TH17 CELLS;

EID: 84973523411     PISSN: 00916749     EISSN: 10976825     Source Type: Journal    
DOI: 10.1016/j.jaci.2015.09.048     Document Type: Article

References (9)

1. T. Korn, E. Bettelli, M. Oukka, and V.K. Kuchroo IL-17 and Th17 cells Annu Rev Immunol 27 2009 485 517
2. C.W. Lees, J.C. Barrett, M. Parkes, and J. Satsangi New IBD genetics: common pathways with other diseases Gut 60 2011 1739 1753
3. P.J. Mease, M.C. Genovese, M.W. Greenwald, C.T. Ritchlin, A.D. Beaulieu, A. Deodhar, and et al. Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis N Engl J Med 370 2014 2295 2306
4. M.C. Genovese, P. Durez, H.B. Richards, J. Supronik, E. Dokoupilova, V. Mazurov, and et al. Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study Ann Rheum Dis 72 2013 863 869
5. W. Hueber, B.E. Sands, S. Lewitzky, M. Vandemeulebroecke, W. Reinisch, P.D. Higgins, and et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial Gut 61 2012 1693 1700
6. Ivanov II, B.S. McKenzie, L. Zhou, C.E. Tadokoro, A. Lepelley, J.J. Lafaille, and et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells Cell 126 2006 1121 1133
7. J.R. Huh, M.W. Leung, P. Huang, D.A. Ryan, M.R. Krout, R.R. Malapaka, and et al. Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORgammat activity Nature 472 2011 486 490
8. S. Xiao, N. Yosef, J. Yang, Y. Wang, L. Zhou, C. Zhu, and et al. Small-molecule RORgammat antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms Immunity 40 2014 477 489
9. J. Skepner, R. Ramesh, M. Trocha, D. Schmidt, E. Baloglu, M. Lobera, and et al. Pharmacologic inhibition of RORgammat regulates Th17 signature gene expression and suppresses cutaneous inflammation in vivo J Immunol 192 2014 2564 2575