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Identification of a Selective RORγ Ligand That Suppresses T(H)17 Cells and Stimulates T Regulatory Cells

Identification of a Selective RORγ Ligand That Suppresses T(H)17 Cells and Stimulates T Regulatory Cells

Laura A Solt, Naresh Kumar, Yuanjun He, Theodore M Kamenecka, Patrick R Griffin, Thomas P Burris

ACS Chem Biol. 2012 Sep 21;7(9):1515-9.

PMID: 22769242

Abstract:

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 (RORα and RORγt) are considered to be the master regulators of development of T(H)17 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 RORγ-specific synthetic ligand, SR1555, that not only inhibits T(H)17 cell development and function but also increases the frequency of T regulatory cells. Our data suggests synthetic RORγ ligands can be developed that target both suppression of T(H)17 and stimulation of T regulatory cells, offering key advantages in development of therapeutics targeting autoimmune diseases.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1386439515	SR1555		1386439-51-5	Price

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