近日，四川大学魏霞蔚小组的研究显示，肺纤维化的免疫肽分析为确定治疗靶点提供了一个平台。2026年4月20日，国际知名学术期刊《自然—免疫学》发表了这一成果。

在这里，课题组研究人员从人类特发性肺纤维化肺外植体和博来霉素处理的小鼠的纤维化灶中鉴定了MHC I类免疫肽，鉴定了多种纤维化相关肽。博莱霉素诱导小鼠肺纤维化的平行分析使治疗靶点的计算优先级成为可能。在体内，三种候选肽（MAF116-124、APBB270-78和TNS319 - 127）的治疗性疫苗有效地减轻了博莱霉素治疗小鼠的纤维化进展。

此外，利用其进化保守性，该课题组人员发现MAF116-124诱导特异性人类细胞毒性T淋巴细胞裂解人类特发性肺纤维化源性肌成纤维细胞和M2样巨噬细胞。这项研究表明，免疫肽球分析为发现可翻译的抗纤维化免疫疗法提供了一个平台。

研究人员表示，纤维化是许多慢性疾病的严重病理结果，然而靶向改变的主要组织相容性复合体（MHC） I类免疫肽穹的治疗潜力仍未得到很大程度的探索。

附：英文原文

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

Author: Bai, Ziyi, Lan, Tianxia, Hong, Weiqi, Que, Haiying, Zhu, Min, Xiao, Xin, Wan, Dandan, Ai, Jiayuan, Huang, Shaoxiong, Wang, Jiayu, Hong, Qiaonan, Liu, Yanyan, Xiao, Chengxin, Zhao, Chengjian, Wang, Xin, Zhang, Xiaolong, Yang, Ting, Xu, Heng, Dai, Lunzhi, Powell, Charles A., Richeldi, Luca, Luo, Fengming, Dong, Haohao, Yuan, Yong, Pu, Qiang, Wei, Xiawei

Issue&Volume: 2026-04-20

Abstract: 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.

DOI: 10.1038/s41590-026-02501-x

Source: https://www.nature.com/articles/s41590-026-02501-x