CD103hi Treg cells constrain lung fibrosis induced by CD103lo tissue-resident pathogenic CD4 T cells
CD103hi Treg cells constrain lung fibrosis induced by CD103lo tissue-resident pathogenic CD4 T cells
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DOI：
10.1038/s41590-019-0494-y
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发表时间：
2019-11-01
影响因子：
30.5
通讯作者：
Nakayama, Toshinori
中科院分区：
文献类型：
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作者：
Ichikawa, Tomomi;Hirahara, Kiyoshi;Nakayama, Toshinori
组织驻留记忆 T 细胞 (T-RM 细胞) 是非淋巴组织中适应性免疫的重要介质。然而，慢性炎症病变中CD4(+) T-RM细胞的功能异质性和致病作用仍然未知。我们发现CD69(hi)CD103(lo)CD4(+)T-RM细胞产生效应细胞因子并促进长期暴露于烟曲霉诱导的炎症和纤维化反应。同时，诱导免疫抑制性CD69(hi)CD103(hi)Foxp3(+)CD4(+)调节性T细胞并限制致病性CD103(lo)T-RM细胞引起纤维化的能力。因此，肺组织驻留的CD4+T细胞在慢性肺部炎症的病理学中起着至关重要的作用，CD103的表达定义了发炎肺中的致病效应细胞和免疫抑制组织驻留细胞亚群。
Tissue-resident memory T cells (T-RM cells) are crucial mediators of adaptive immunity in nonlymphoid tissues. However, the functional heterogeneity and pathogenic roles of CD4(+) T-RM cells that reside within chronic inflammatory lesions remain unknown. We found that CD69(hi)CD103(lo) CD4(+) T-RM cells produced effector cytokines and promoted the inflammation and fibrotic responses induced by chronic exposure to Aspergillus fumigatus. Simultaneously, immunosuppressive CD69(hi)CD103(hi)Foxp3(+) CD4(+) regulatory T cells were induced and constrained the ability of pathogenic CD103(lo) T-RM cells to cause fibrosis. Thus, lung tissue-resident CD4(+) T cells play crucial roles in the pathology of chronic lung inflammation, and CD103 expression defines pathogenic effector and immunosuppressive tissue-resident cell subpopulations in the inflamed lung.