PDF(Pubmed)
Abstract：
Excessive inflammation is a postulated cause of severe disease and death in respiratory virus infections. In response to severe influenza virus infection, adoptively transferred naïve hemagglutinin-specific CD4+ T cells from CD4+ TCR-transgenic 6.5 mice drive an IFN-γ-producing Th1 response in wild-type mice. It helps in virus clearance but also causes collateral damage and disease aggravation. The donor 6.5 mice have all the CD4+ T cells with TCR specificity toward influenza hemagglutinin. Still, the infected 6.5 mice do not suffer from robust inflammation and grave outcome. The initial Th1 response wanes with time, and a prominent Th17 response of recent thymic emigrants alleviates inflammation and bestows protection in 6.5 mice. Our results suggest that viral neuraminidase-activated TGF-β of the Th1 cells guides the Th17 evolution, and IL-17 signaling through the non-canonical IL-17 receptor EGFR activates the scaffold protein TRAF4 more than TRAF6 during alleviation of lung inflammation in severe influenza.
摘要：
过度炎症是呼吸道病毒感染中严重疾病和死亡的假定原因。为了应对严重的流感病毒感染，来自CD4+TCR转基因6.5小鼠的过继转移的原初血凝素特异性CD4+T细胞在野生型小鼠中驱动产生IFN-γ的Th1应答。它有助于病毒清除，但也会导致附带损害和疾病加重。供体6.5小鼠具有对流感血凝素具有TCR特异性的所有CD4+T细胞。尽管如此，感染的6.5小鼠不遭受强烈的炎症和严重的结果。最初的Th1响应随着时间的推移而减弱，最近胸腺移民的突出Th17反应减轻了炎症并赋予6.5小鼠保护作用。我们的结果表明，Th1细胞的病毒神经氨酸酶激活的TGF-β指导Th17进化，和IL-17信号通过非典型IL-17受体EGFR在缓解严重流感的肺部炎症期间比TRAF6更激活支架蛋白TRAF4。
