IL-17 production by tissue-resident MAIT cells is locally induced in children with pneumonia
IL-17 production by tissue-resident MAIT cells is locally induced in children with pneumonia
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肺炎儿童局部诱导组织驻留 MAIT 细胞产生 IL-17
DOI：
10.1038/s41385-020-0273-y
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发表时间：
2020-02-28
影响因子：
8
通讯作者：
Lu, Gen
中科院分区：
文献类型：
--
作者：
Lu, Bingtai;Liu, Ming;Lu, Gen
社区获得性肺炎是造成5岁以下儿童发病率和死亡率的主要原因。在检查患有CAP的儿童的支气管肺泡灌洗（BALs）时，我们发现白细胞介素-17 （IL-17）的产生在严重的CAP中显着增加。免疫分析显示，来自BALs的粘膜相关不变T （MAIT）细胞，而不是来自CAP患者的血液，积极产生IL-17 （MAIT17）。单细胞rna测序显示，MAIT17位于bal驻留PLZFhiCD103+MAIT亚群中，高表达缺氧诱导因子1α (HIF-1α)，反映了炎症组织的缺氧状态。CAP bal还含有一个T-bet+MAIT1亚群和一个新的低表达HIF1A的DDIT3+（DNA损伤诱导转录物3阳性）MAIT亚群。此外，MAIT17在与组织定位、先天性和细胞毒性相关的基因表达方面与t -辅助型17 （Th17）细胞不同。最后，我们发现BAL单核细胞具有高炎症性并诱导MAIT17分化。因此，组织驻留的MAIT17细胞在感染的呼吸道粘膜被诱导，可能受到炎症单核细胞的影响，并在CAP期间参与il -17介导的炎症。
Community-acquired pneumonia (CAP) contributes substantially to morbidity and mortality in children under the age of 5 years. In examining bronchoalveolar lavages (BALs) of children with CAP, we found that interleukin-17 (IL-17) production was significantly increased in severe CAP. Immune profiling showed that mucosal-associated invariant T (MAIT) cells from the BALs, but not blood, of CAP patients actively produced IL-17 (MAIT17). Single-cell RNA-sequencing revealed that MAIT17 resided in a BAL-resident PLZFhiCD103+MAIT subset with high expression of hypoxia-inducible factor 1α (HIF-1α), reflecting the hypoxic state of the inflamed tissue. CAP BALs also contained a T-bet+MAIT1 subset and a novel DDIT3+(DNA damage-inducible transcript 3-positive) MAIT subset with low expression of HIF1A. Furthermore, MAIT17 differed from T-helper type 17 (Th17) cells in the expression of genes related to tissue location, innateness, and cytotoxicity. Finally, we showed that BAL monocytes were hyper-inflammatory and elicited differentiation of MAIT17. Thus, tissue-resident MAIT17 cells are induced at the infected respiratory mucosa, likely influenced by inflammatory monocytes, and contribute to IL-17-mediated inflammation during CAP.