Identification of a selective ROR gamma ligand that suppresses T(H)17 cells and stimulates T regulatory cells

Academic Article
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publication date

  • September 2012

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 (ROR? and ROR?t) 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 ROR?-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 ROR? 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.
  • 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.