Vaccine-induced Th17 cells are established as resident memory cells in the lung and promote local IgA responses
Vaccine-induced Th17 cells are established as resident memory cells in the lung and promote local IgA responses
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DOI：
10.1038/mi.2016.28
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发表时间：
2017-01-01
影响因子：
8
通讯作者：
Andersen, P.
中科院分区：
文献类型：
--
作者：
Christensen, D.;Mortensen, R.;Andersen, P.
加速和有效的粘膜免疫反应的能力对于预防许多感染的发生至关重要。免疫球蛋白 A (IgA) 的分泌是第一道防线的关键组成部分，但其潜在的细胞机制仍不完全清楚。我们评估了不同的免疫途径，并检查了气道粘膜中 IgA 诱导的要求。我们证明，用 T 辅助细胞 (Th) 17 诱导佐剂中的重组抗原进行皮下启动，然后进行气道加强，可促进肺部 IgA 的高且持续水平。这种反应与肺引流淋巴结中生发中心的形成有关。肺部 IgA 反应依赖于 Th17 细胞，如果白细胞介素 (IL)-17 耗尽或用仅诱导 Th1 或 Th2 反应的疫苗启动时，肺部 IgA 反应就会消失。我们使用血管内染色来证明 IgA+ B 细胞和趋化因子受体 6 (CCR6)+Th17 细胞在气道加强免疫后被募集到肺实质。一旦被招募到肺实质，Th17 细胞就会转化为常驻淋巴细胞，并在肺组织中持续存在至少 10 周。在这里，它们促进 T 细胞和 B 细胞的加速募集，从而加速对第二次气道加强免疫的 IgA 召回反应。
The ability to mount accelerated and efficient mucosal immune responses is critically important to prevent the establishment of many infections. Secretion of immunoglobulin A (IgA) is a key component in this first line of defense, but the underlying cellular mechanisms are still not completely understood. We have evaluated different routes of immunization and examined the requirements for IgA induction in the airway mucosa. We demonstrate that subcutaneous priming with a recombinant antigen in a T helper (Th) 17-inducing adjuvant followed by airway boosting promotes high and sustained levels of IgA in the lungs. This response is associated with germinal center formation in the lung-draining lymph nodes. The lung IgA response is dependent on Th17 cells and absent if interleukin (IL)-17 is depleted or when priming with vaccines inducing only Th1 or Th2 responses. We used intravascular staining to demonstrate that IgA+ B cells and chemokine receptor 6 (CCR6)+Th17 cells are recruited to the lung parenchyma after the airway booster immunization. Once recruited to the lung parenchyma, the Th17 cells transform into resident lymphocytes that persist in the lung tissue for at least 10 weeks. Here, they facilitate the accelerated recruitment of T and B cells resulting in an accelerated IgA recall response to a second airway booster immunization.