Retinoid-related orphan nuclear receptor gamma t (RORγt)

Retinoid-related orphan nuclear receptor gamma t (RORγt) is a lineage-defining member of the nuclear receptor family, acting as a transcription factor critical for the development and differentiation of Th17 cells, which produce the pro-inflammatory cytokine IL-17. RORγt is mostly expressed in the thymus, lymphoid tissue inducer cells, Th17 cells, and other innate lymphoid cells, orchestrating immune responses against pathogens and contributing to tissue inflammation. Dysregulation of RORγt activity is central in the pathogenesis of autoimmune and inflammatory diseases, making it a highly attractive drug target—both through inhibition (with antagonists/inverse agonists) for autoimmune conditions and potentially activation (with agonists) for boosting immune responses in cancer or infections. Selective RORγt inhibitors are in development, with safety risks related mainly to immune suppression and infection susceptibility.

Other names

RAR-related orphan receptor gamma tRORγtRORgammatRetinoic acid receptor-related orphan receptor gamma tRORC2 isoform

Inverse agonism or antagonism leads to inhibition of Th17 cell differentiation and decreased IL-17/interleukin-22 production, thereby suppressing inflammation and autoimmunity. Agonism theoretically could stimulate immunity for infections or cancer therapy.