RORC2: The master of human Th17 cell programming

it is now recognized that Th17 cells constitute the third effector arm of Th cells, complementing the Th1 and Th2 lineages. Although secretion of IL-17 is a primary defining characteristic of Th17 cells, the expression profile of specific chemokine receptors, cell surface molecules and cytokines are also part of the Th17 cell differentiation program. The orphan nuclear receptor ROR gamma t/RORC2 (mice/humans) is the master transcription factor that can drive Th17 cell differentiation in both mice and humans; however, it is not completely clear how much of the human Th17 lineage function and phenotype can be recapitulated by only RORC2 expression. In this issue of the European Journal of Immunology, a study reports that ectopic expression of RORC2 in primary human T cells induces, in addition to IL-17 production, a cytokine and chemokine receptor profile consistent with bona fide human Th17 cells. In addition, programming of human Th17 cells by RORC2 results in partial resistance of these T cells to suppression by Tregs. These findings support the notion that RORC2 is a master switch that initiates a wide range of phenotypic and functional programming during Th17 cell differentiation.