Small-Molecule RORγt Antagonists: One Stone Kills Two Birds.

Although small-molecule thymus-specific isoform of retinoic acid receptor-related orphan nuclear receptor γ (RORγt) antagonists suppressing interleukin (IL)-17-producing T helper (Th17) cells are widely reported, the effect of these molecules on other RORγt-expressing cells is unknown. However, a new study reports that RORγt inhibition in CD4+CD8+ thymocytes resulted in skewed T cell repertoire, contributing to a reduction in the frequency of self-reactive T cells and resistance to autoimmunity.