Cutting Edge: Opposite Effects of IL-1 and IL-2 on the Regulation of IL-17+ T Cell Pool IL-1 Subverts IL-2-Mediated Suppression

In this report, we show that IL-17(+)CD4(+) and IL-17(+)CD8(+) T cells are largely found in lung and digestive mucosa compartments in normal mice. Endogenous and exogenous IL-1 dramatically contribute to IL-17(+) T cell differentiation mediated by TGFbeta and IL-6. IL-1 is capable of stimulating IL-17(+) T cell differentiation in the absence of IL-6. Furthermore, although IL-2 reduces IL-17(+) T cell differentiation, IL-1 completely disables this effect. Mechanistically, IL-1 and IL-2 play opposite roles in regulating the expression of several molecules regulating Th17 cell differentiation, including the orphan nuclear receptor ROR gamma t, the IL-1 receptor, and the IL-23 receptor. IL-1 subverts the effects of IL-2 on the expression of these gene transcripts. Altogether, our work demonstrates that IL-6 is important but not indispensable for IL-17(+) T cell differentiation and that IL-1 plays a predominant role in promoting IL-17(+) T cell induction. Thus, the IL-17(+) T cell pool may be controlled by the local cytokine profile in the microenvironment.