IL-2 phosphorylates STAT5 to drive IFN-γ production and activation of human dendritic cells

IL-2 磷酸化 STAT5 以驱动 IFN-γ 的产生和人类树突状细胞的激活

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作者:Florence Herr, Roxane Lemoine, Fabrice Gouilleux, Daniel Meley, Ihab Kazma, Audrey Heraud, Florence Velge-Roussel, Christophe Baron, Yvon Lebranchu

Abstract

Human dendritic cells (hDCs) produce IL-2 and express IL-2R α-chain (CD25), but the role of IL-2 in DC functions is not well defined. A recent study suggested that the main function of CD25 on hDCs was to transpresent IL-2 to activate T lymphocytes. Our results demonstrate the expression of the three chains of the IL-2R on hDCs and that IL-2 induces STAT5 phosphorylation. Interestingly, use of inhibitors of p-STAT5 revealed that IL-2 increases LPS-induced IFN-γ through STAT5 phosphorylation. Finally, we report that IL-2 increases the ability of hDCs to activate helpless CD8(+) T cells, most likely because of IL-2-triggered IFN-γ synthesis, as we previously described. For the first time, to our knowledge, we disclose that IL-2 induces monocyte-derived hDC's functional maturation and activation through IL-2R binding. Interestingly, our study suggests a direct effect of anti-CD25 mAbs on hDCs that may contribute to their clinical efficacy.

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