Jiang Li, Yao Shuyu, Huang Su, Wright Jeffrey, Braciale Thomas J, Sun Jie
Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
Eur J Immunol. 2016 Dec;46(12):2778-2788. doi: 10.1002/eji.201646548. Epub 2016 Nov 9.
Recent 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.
最近的证据表明，产生白细胞介素-10（IL-10）的效应性CD8 T细胞在急性病毒感染期间调节过度炎症反应中发挥重要作用。然而，调节产生IL-10的效应性CD8 T细胞发育的细胞和分子线索尚未完全明确。在此，我们表明，I型干扰素（IFN）在小鼠流感病毒感染期间对于产生IL-10的效应性CD8 T细胞的发育是必需的。我们发现I型IFN可增强肺部抗原呈递细胞（APC）产生IL-27，从而通过一种CD8 T细胞非自主性方式促进产生IL-10的CD8 T细胞发育。令人惊讶的是，我们还证明CD8 T细胞中的直接I型IFN信号传导对于产生IL-10的CD8 T细胞的最大生成是必需的。CD8 T细胞中的I型IFN信号传导与IL-27和IL-2信号传导协同作用，促进并维持干扰素调节因子4（IRF4）和B淋巴细胞诱导成熟蛋白1（Blimp-1）的表达，这是效应性CD8 T细胞产生IL-10所需的两个转录因子。我们的数据揭示了先天性抗病毒效应细胞因子在呼吸道病毒感染期间调节效应性CD8 T细胞产生调节性细胞因子中的关键作用。
