A novel isoform of the orphan receptor RORγt suppresses IL-17 production in human T cells

T helper (Th)17 cells constitute a distinct subset of CD4(+) helper T cells that is mainly characterized by abundant interleukin (IL)-17 production and is involved in the host defence against bacteria and fungi as well as in the pathogenesis of autoimmune diseases. The retinoic orphan receptor (ROR)gamma t directs the transcriptional activation of the IL17 gene. Here, we report the presence of a novel ROR gamma t isoform, ROR gamma t-Delta(5-8), which lacks the hinge-encoding exons 5-8 and represses potently IL17 and IL21 gene transcription. It thereby reduces the expression of multiple Th17-assigned cytokines. We propose that ROR gamma t-Delta(5-8) acts as a dominant-negative regulator of ROR gamma t-mediated gene regulation and the balance between the full-length ROR gamma t and the novel repressor isoform may arbitrate IL-17 production in human T cells.