RORγt is an isoform of the orphan nuclear receptor RORγ (differing by 24 amino acids in the N terminal domain) which is selectively expressed in white blood cells. In response to the presence of interleukin 6, TGF and other cytokines, the expression of RORγt is turned on in naïve T cells, and controls the expression of the interleukin 23 receptor which is critical for the proliferation of pathogenic Th17 cells in response to interleukin 23 (see below).
The differentiation and expansion of Th17 and innate lymphoid cells cells at sites of autoimmune inflammation is driven by a combination of cytokines, including interleukin 23, which stimulate production of a number of pathogenic factors such as interleukin 17A-F and interleukin 22.
RORγt controls expression of the interleukin 23 receptor, and mice which are deficient in RORγt have reduced Th17 cell activation and are resistant to the development of experimental allergic encephalomyelitis, colitis and psoriasis-like lesions induced by the intradermal injection of interleukin 23.
Although interleukin 17 is not the only cytokine under control of RORγt, antibodies that selectively block IL-17 or the IL-17 receptor have shown remarkable levels of efficacy in the clinic.