Identification of a Selective ROR纬 Ligand That Suppresses TH17 Cells and Stimulates T Regulatory Cells

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• 作者：Laura A. Solt ; Naresh Kumar ; Yuanjun He ; Theodore M. Kamenecka ; Patrick R. Griffin ; Thomas P. Burris
• 刊名：ACS Chemical Biology
• 出版年：2012
• 出版时间：September 21, 2012
• 年：2012
• 卷：7
• 期：9
• 页码：1515-1519
• 全文大小：304K
• 年卷期：v.7,no.9(September 21, 2012)
• ISSN：1554-8937

文摘

Nuclear receptors (NRs) are ligand-regulated transcription factors, many of which are validated targets for clinical purposes. The retinoic acid receptor-related orphan nuclear receptors alpha and gamma t (ROR伪 and ROR纬t) are considered to be the master regulators of development of T_H17 cells, a subset of T cells that have been implicated in the pathology of several autoimmune diseases, including multiple sclerosis (MS) and rheumatoid arthritis (RA). We report here the identification of a novel ROR纬-specific synthetic ligand, SR1555, that not only inhibits T_H17 cell development and function but also increases the frequency of T regulatory cells. Our data suggests synthetic ROR纬 ligands can be developed that target both suppression of T_H17 and stimulation of T regulatory cells, offering key advantages in development of therapeutics targeting autoimmune diseases.