Comprehensive profiling of smoke-induced T cells in mice implicates clonal γδT17 cells as a hallmark of COPD

作者：Xinyue Mei, Junxiang Wang, Yuan Wang, Cheng Li, Xiaoyu Wang, Xinyuan Liu, Ge Bai, Jiaying Zhong, Mingzhu Huang, Suyin Huang, Peiyu Huang, Jieda Cui, Yü Liu, Qianmei Wen, Ruiting Sun, Erkang Yi, Fan Wu, Xiaohui Wu, Ziqing Yuan, Qi Wan, Xiaoyang Zheng, Yujie Zuo, Jingwei Zhang, Leqing Zhu, Yumin Zhou, Zhongfang Wang, Pixin Ran · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-67120-w · 被引用次数：2 · 研究领域：Chronic Obstructive Pulmonary Disease (COPD) Research、T-cell and B-cell Immunology、Pediatric health and respiratory diseases

The mechanisms of the chronic inflammatory response in smoking-induced chronic obstructive pulmonary disease (COPD) remain unclear, with limited understanding of T cell responses to smoke exposure in lung tissue and circulation. We characterized the alterations in T cells associated with smoke exposure using single-cell RNA sequencing, TCR sequencing, and flow cytometry-based validation. Our experiments show significant recruitment of T cells within the airways, exhibiting a multifaceted immune profile, augmented TCR clonal diversity, and a prolonged CDR3 length. Notably, smoke-induced γδ T cells, particularly clonally expanded γ6δ4 T cells with high Il17a expression, accumulate in smoke-induced airway inflammation. Despite arising in inflammation, these cells function in a protective manner: γδT17 deficiency worsens smoke-induced lung injury, whereas adoptive transfer of γδT17 cells restores tissue protection in smoke-exposed lungs over time. Here, we show γδT17 cells as a potential target for addressing smoke-induced immune dysfunctions, providing alternative avenues for early prevention and treatment of COPD. T cells have been shown to have a function in chronic lung inflammation in COPD. Here the authors characterise the single cell transcriptional profile of T cells after smoke inhalation in mouse models showing changes in TCR repertoire and Il17a expression in γδ T cells, suggesting smoke-associated γδ T cells are involved in COPD inflammation and implicating γδT17 cell...