Immunopeptidome profiling in pulmonary fibrosis provides a platform for identifying therapeutic targets

作者：Ziyi Bai, Tianxia Lan, Weiqi Hong, Haiying Que, Min Zhu, XJ Xiao, Dandan Wan, Jiayuan Ai, Huang, Jiayu Wang, Qiaonan Hong, Liu Y, Chengxin Xiao, Chengjian Zhao, Xin Wang, Xi Zhang, Ting Yang, Heng Xu, Lunzhi Dai, Charles A. Powell, Luca Richeldi, Fengming Luo, Haohao Dong, 袁勇, Qiang Pu, Xiawei Wei · 发表于：Nature Immunology · 年份：2026 · DOI：10.1038/s41590-026-02501-x · 被引用次数：2 · 研究领域：vaccines and immunoinformatics approaches、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Chemokine receptors and signaling

Fibrosis is a severe pathological outcome of many chronic diseases, yet the therapeutic potential of targeting the altered major histocompatibility complex (MHC) class I immunopeptidome remains largely unexplored. Here we characterized the MHC class I immunopeptidomes from both fibrotic foci of human idiopathic pulmonary fibrosis lung explants and bleomycin-treated mice, identifying a diverse repertoire of fibrosis-associated peptides. Parallel profiling of bleomycin-induced pulmonary fibrosis in mice enabled the computational prioritization of therapeutic targets. In vivo, therapeutic vaccination with three candidate peptides (MAF116–124, APBB270–78 and TNS3119–127) effectively mitigated fibrosis progression in bleomycin-treated mice. Furthermore, leveraging its evolutionary conservation, we found that MAF116–124 elicited specific human cytotoxic T lymphocytes that lysed human idiopathic pulmonary fibrosis-derived myofibroblasts and M2-like macrophages. This study indicates that immunopeptidome profiling provides a robust platform for discovering translatable antifibrotic immunotherapies. Wei and colleagues characterized the MHC class I immunopeptidome in mice and humans with lung fibrosis and identified immunogenic peptides specifically expressed in fibrosis-associated lung cell subsets that blocked the progression of fibrosis in mice treated with bleomycin.