IL-17A Promotes Pulmonary B-1a Cell Differentiation via Induction of Blimp-1 Expression during Influenza Virus Infection.
IL-17A Promotes Pulmonary B-1a Cell Differentiation via Induction of Blimp-1 Expression during Influenza Virus Infection.
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IL-17A 在流感病毒感染期间通过诱导 Blimp-1 表达促进肺 B-1a 细胞分化
DOI：
10.1371/journal.ppat.1005367
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发表时间：
2016-01
期刊：
影响因子：
6.7
通讯作者：
Lu L
中科院分区：
文献类型：
--
作者：
Wang X;Ma K;Chen M;Ko KH;Zheng BJ;Lu L
B-1细胞通过产生天然IgM抗体，在流感感染的早期保护中发挥关键作用。然而，调控这一过程的潜在机制在很大程度上是未知的。在流感感染期间，我们发现胸膜腔B-1a细胞迅速浸润肺部，在那里它们进行浆细胞分化，并增强IgM的产生。在B-1a细胞中，IL-17A信号通路通过诱导Blimp-1表达和NF-κB活化来促进这一过程。IL-17A的缺乏导致呼吸道中b -1a衍生抗体的产生严重受损，导致病毒清除能力不足。b -1a来源的天然抗体的转移使Il17a -/-小鼠免于致命的感染。总之，我们确定了IL-17A在促进B-1a细胞浆细胞分化中的关键功能。我们的研究结果为肺B-1a细胞对流感感染反应的调节机制提供了新的见解。
B-1 cells play a critical role in early protection during influenza infections by producing natural IgM antibodies. However, the underlying mechanisms involved in regulating this process are largely unknown. Here we found that during influenza infection pleural cavity B-1a cells rapidly infiltrated lungs, where they underwent plasmacytic differentiation with enhanced IgM production. This process was promoted by IL-17A signaling via induction of Blimp-1 expression and NF-κB activation in B-1a cells. Deficiency of IL-17A led to severely impaired B-1a-derived antibody production in the respiratory tract, resulting in a deficiency in viral clearance. Transfer of B-1a-derived natural antibodies rescued Il17a -/- mice from otherwise lethal infections. Together, we identify a critical function of IL-17A in promoting the plasmacytic differentiation of B-1a cells. Our findings provide new insights into the mechanisms underlying the regulation of pulmonary B-1a cell response against influenza infection.