title: Identification of a selective RORγ ligand that suppresses T(H)17 cells and stimulates T regulatory cells.
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.
authors: The Scripps Research Institute, Jupiter, FL 33458, USA.
authors: Laura A
authors: LA
authors: Solt
authors: Naresh
authors: N
authors: Kumar
authors: Yuanjun
authors: Y
authors: He
authors: Theodore M
authors: TM
authors: Kamenecka
authors: Patrick R
authors: PR
authors: Griffin
authors: Thomas P
authors: TP
authors: Burris
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D055808:Drug Discovery; D057809:HEK293 Cells; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology*; D013449:Sulfonamides / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D020381:Interleukin-17; D008024:Ligands; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C558809:SR1001; D013449:Sulfonamides; D013844:Thiazoles