Journal of Clinical and Cellular Immunology
Open Access

RORγt inverse agonists suppress Th17 cell differentiation in vivo

2^nd International Conference on Clinical & Cellular Immunology

October 15-17, 2013 Hampton Inn Tropicana, Las Vegas, NV, USA

Jianfei Yang

Scientific Tracks Abstracts: J Clin Cell Immunol

Abstract :

Th17 cells play a critical role in the pathogenesis of autoimmune diseases. Differentiation of Th17 cells requires the nuclear receptor ROR γ t, and inhibition of ROR γ t by small molecule inhibitors prevents Th17 cell differentiation in vitro . ROR γ t inhibitors also modulate ROR γ t activity in vivo as demonstrated by a significant reduction in the severity of experimental autoimmune encephalomyelitis. However, the effect of ROR γ t small molecule inhibitors on the in vivo generation of Th17 cells has not yet been clearly demonstrated. Here we report a novel, potent, and selective ROR γ t inverse agonist TMP778 and demonstrate its role in the in vivo differentiation of Th17 cells. TMP778 blocks both human and mouse Th17 cell differentiation in vitro. In vivo , administration of TMP778 to C57BL/6 mice immunized with myelin oligodendrocyte peptide 35-55 (MOG 35- 55 ) blocked MOG-specific IL-17A expression. In addition, expression of Th17 signature genes ( Il17a, Il17f, Il22 , and CCL20 ) as well as Ifn γ was inhibited. Further, IL-17-producing CD4 + T cells were significantly reduced in IL-17-IRES-GFP transgenic mice administrated TMP778 after immunization with MOG 35-55 . Thus, our studies demonstrate that ROR γ t inverse agonist TMP778 suppress Th17 differentiation in vivo .

Biography :

Jianfei Yang is a Principal Scientist and a Project Leader of a Th17 cell-related project at Tempero Pharmaceuticals, a GSK company, in Cambridge, MA, USA. He received a Ph.D. in Pathology from Niigata University in Japan in 1997. He then obtained postdoctoral training in Dr. Ken Murphy?s lab at HHMI and Washington University. In the past 16 year, he has been studying the role of CD4 + T helper cells in immunity and diseases. He has more than 10 years of experience in autoimmune disease research and pharmaceutical drug development. He has published numerous papers and patents.