Jiang, LiYao, ShuyuHuang, SuWright, JeffreyBraciale, Thomas J.Sun, Jie2018-06-082018-06-082016-12Jiang, L., Yao, S., Huang, S., Wright, J., Braciale, T. J., & Sun, J. (2016). Type I interferon signaling facilitates the development of IL-10-producing effector CD8+ T cells during influenza virus infection. European Journal of Immunology, 46(12), 2778. https://doi.org/10.1002/eji.201646548https://hdl.handle.net/1805/16423Recent evidence has suggested that IL-10-producing effector CD8+ T cells play an important role in regulating excessive inflammation during acute viral infections. However, the cellular and molecular cues regulating the development of IL-10-producing effector CD8+ T cells are not completely defined. Here, we show that type I interferons (IFNs) are required for the development of IL-10-producing effector CD8+ T cells during influenza virus infection in mice. We find that type I IFNs can enhance IL-27 production by lung APCs, thereby facilitating IL-10-producing CD8+ T-cell development through a CD8+ T-cell-nonautonomous way. Surprisingly, we also demonstrate that direct type I IFN signaling in CD8+ T cells is required for the maximal generation of IL-10-producing CD8+ T cells. Type I IFN signaling in CD8+ T cells, in cooperation with IL-27 and IL-2 signaling, promotes and sustains the expression of IFN regulatory factor 4 (IRF4) and B-lymphocyte-induced maturation protein-1 (Blimp-1), two transcription factors required for the production of IL-10 by effector CD8+ T cells. Our data reveal a critical role of the innate antiviral effector cytokines in regulating the production of a regulatory cytokine by effector CD8+ T cells during respiratory virus infection.en-USPublisher PolicyCD8+ T cellsIL-10IL-27InfluenzaType I IFNArticle