Interferon regulatory factor 3 controls interleukin-17 expression in CD8 T lymphocytes

作者：Laure Ysebrant de Lendonck, Sandrine Tonon, Muriel Nguyen, Patricia Vandevenne, Iain Welsby, Valérie Martinet, Céline Molle, Louis‐Marie Charbonnier, Oberdan Léo, Stanislas Goriely · 发表于：Proceedings of the National Academy of Sciences · 年份：2013 · DOI：10.1073/pnas.1219221110 · 被引用次数：32 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Cytokine Signaling Pathways and Interactions

IFN regulatory factor (IRF) 3 plays a key role in innate responses against viruses. Herein we assessed its contribution to T-cell activation. We observed that poly(I:C)-induced IRF3 activation in CD8 T cells represses IL-17 expression in a type I IFN-independent fashion. Even in the absence of poly(I:C), polyclonally activated naïve IRF3(-/-) CD8 T cells expressed high levels of IL-17 and IL-23R in comparison with wild-type cells. Furthermore, IRF3(-/-) OT1 cells adoptively transferred into wild-type hosts also produced higher IL-17 levels upon immunization than their wild-type counterparts. This phenotype could be reversed by ectopic expression of IRF3, confirming that this effect is intrinsic to T cells. We show that IRF3 directly interacts with RORγt in the cytoplasm through its IRF interaction domain and limits its ability to bind and transactivate the IL-17 promoter. These observations uncover an unexpected role of IRF3 in the control of CD8 T-cell polarization.