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The role of T cells in heart failure has been increasingly recognized, but whether programmed cell death protein 1 (PD1\n                    <jats:sup>+<\/jats:sup>\n                    ) T cells modulate cardiac fibrosis during the post-MI pathological remodeling process remains unclear. Single-cell RNA sequencing and mass cytometry were conducted to determine the proportion of PD1\n                    <jats:sup>+<\/jats:sup>\n                    T cells in both human ischemic diseases and a mouse MI model. Bulk RNA sequencing and cytokine arrays were used to investigate the function of PD1\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Cardiac function and histology were evaluated in non-human primates and rodents post-MI. We observed significant enrichment of PD1\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the heart after MI, which was positively associated with cardiac fibroblast activation and, hence, collagen secretion. Unlike in tumors, PD1\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the heart after MI demonstrated activated characteristics. PD1 knockout mice exhibited reduced cardiac fibrosis, resulting in increased cardiac performance following MI. Mechanistically, activated PD1\n                    <jats:sup>+<\/jats:sup>\n                    T cells were found to drive fibrosis remodeling by modulating the CXCL9\/CXCR3 axis through direct interaction with cardiac fibroblasts \u2014 an effect that occurred independently of the PD1\/programmed death-ligand 1 (PD-L1) signaling pathway. Notably, anti-PD1 therapy in both mouse and non-human primate MI models effectively attenuated fibrosis and improved cardiac function without eliciting detectable adverse effects in non-cardiac organs. Our findings reveal a distinct PD-L1-independent pro-fibrotic mechanism mediated by PD1\n                    <jats:sup>+<\/jats:sup>\n                    T cells during post-MI cardiac remodeling. Therapeutic inhibition of PD1\n                    <jats:sup>+<\/jats:sup>\n                    T cells effectively suppressed fibrosis progression, highlighting its potential as an immunotherapeutic target for post-MI cardiac repair.\n                  <\/jats:p>","DOI":"10.1038\/s41421-026-00924-2","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:10:15Z","timestamp":1791303015000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Blocking PD1 prevents T-cell-promoted fibrosis in myocardial infarction"],"prefix":"10.1038","volume":"12","author":[{"given":"Xiaoying","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changchen","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changle","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhua","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9915-1348","authenticated-orcid":false,"given":"Mo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feimu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayue","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyuan","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingju","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhan","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianpeng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2019an","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"924_CR1","first-page":"62","volume":"106","author":"PS Azevedo","year":"2016","unstructured":"Azevedo, P. 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