NK Cells Alleviate Lung Inflammation by Negatively Regulating Group 2 Innate Lymphoid Cells
NK Cells Alleviate Lung Inflammation by Negatively Regulating Group 2 Innate Lymphoid Cells
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NK 细胞通过负向调节第 2 组先天淋巴细胞来缓解肺部炎症
DOI：
10.4049/jimmunol.1601830
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发表时间：
2017-04-15
影响因子：
4.4
通讯作者：
Wan, Xiaochun
中科院分区：
文献类型：
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作者：
Bi, Jiacheng;Cui, Lulu;Wan, Xiaochun
第二组天然淋巴样细胞(ILC2s)在协调II型免疫应答中起着重要作用。然而，第二组先天淋巴样细胞调节的细胞机制仍然知之甚少。在本研究中，我们发现激活的NK细胞通过干扰素-γ在体外抑制了ILC2的增殖以及IL-5和IL-13的产生。此外，在ILC2在肝脏扩张的小鼠模型中，NK细胞激活剂多肌苷多胞酸抑制ILC2的增殖、IL-5和IL-13的产生以及嗜酸性粒细胞的募集。在NK细胞耗竭的小鼠和干扰素-伽马缺乏的小鼠中，多肌苷-多胞苷的这种作用被取消。过继地将野生型NK细胞转移到NK细胞耗竭的小鼠体内，IL-33诱导的ILC2比转移干扰素-g缺陷的NK细胞少。重要的是，在木瓜酶或博莱霉素诱导的肺部炎症的早期阶段，NK细胞的耗竭导致ILC2数量的增加和ILC2产生的细胞因子的增加，并加重了嗜酸性粒细胞增多和杯状细胞的增生。总之，这些数据表明，在肺部炎症的早期阶段，NK细胞负向调节ILC2，这代表了ILC的两个家族成员之间的新的细胞相互作用。
Group 2 innate lymphoid cells (ILC2s) play an important role in orchestrating type II immune responses. However, the cellular mechanisms of group 2 innate lymphoid cell regulation remain poorly understood. In this study, we found that activated NK cells inhibited the proliferation of, as well as IL-5 and IL-13 production by, ILC2s in vitro via IFN-gamma. In addition, in a murine model of ILC2 expansion in the liver, polyinosinic-polycytidylic acid, an NK cell-activating agent, inhibited ILC2 proliferation, IL-5 and IL-13 production, and eosinophil recruitment. Such effects of polyinosinic-polycytidylic acid were abrogated in NK cell-depleted mice and in IFN-gamma-deficient mice. Adoptively transferring wild-type NK cells into NK cell-depleted mice resulted in fewer ILC2s induced by IL-33 compared with the transfer of IFN-g-deficient NK cells. Importantly, during the early stage of papain-or bleomycin-induced lung inflammation, depletion of NK cells resulted in increased ILC2 numbers and enhanced cytokine production by ILC2s, as well as aggravated eosinophilia and goblet cell hyperplasia. Collectively, these data show that NK cells negatively regulate ILC2s during the early stage of lung inflammation, which represents the novel cellular interaction between two family members of ILCs.