The pro‐Th2 cytokine IL‐33 directly interacts with invariant NKT and NK cells to induce IFN‐γ production

IL‐33 has recently been identified as a cytokine endowed with pro‐Th2 functions, raising the question of its effect on invariant natural killer T cell (iNKT), which are potent IL‐4 producers. Here, we report a two‐fold increase of iNKT‐cell counts in spleen and liver after a 7‐day treatment of mice with IL‐33, which results from a direct effect, given that purified iNKT cells express the T1/ST2 receptor constitutively and respond to IL‐33 by in vitro expansion and functional activation. Conversely to the expected pro‐Th2 effect, IL‐33 induced a preferential increase in IFN‐γ rather than IL‐4 production upon TCR engagement that depended on endogenous IL‐12. Moreover, in combination with the pro‐inflammatory cytokine IL‐12, IL‐33 enhanced IFN‐γ production by both iNKT and NK cells. Taken together these data support the conclusion that IL‐33 can contribute as a co‐stimulatory factor to innate cellular immune responses.

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