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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 Suppression¹

Ilona Kryczek^*, Shuang Wei^*, Linhua Vatan^*, June Escara-Wilke, Wojciech Szeliga^*, Evan T. Keller and Weiping Zou^2,*

^* Department of Surgery and Department of Urology, University of Michigan, Ann Arbor, MI 48109

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 TGF 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 RORt, 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-1plays 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the National Cancer Institute (to W.Z.).

² Address correspondence and reprint requests to Dr. Weiping Zou, C560B Medical Science Research Building II, Ann Arbor, MI 48109. E-mail address: wzou{at}umich.edu