{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:25:08Z","timestamp":1786116308783,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82574132"],"award-info":[{"award-number":["82574132"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82504445"],"award-info":[{"award-number":["82504445"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025M770751"],"award-info":[{"award-number":["2025M770751"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Emphysema is the primary pathological feature of chronic obstructive pulmonary disease (COPD). The accumulation of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells induces epithelial cell damage, thereby impairing the pulmonary alveolar niche. In this study, we demonstrated that CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation was associated with COPD progression. Furthermore, our data indicated that AARS1\u2010mediated lactylation was involved in cigarette smoke extract (CSE)\u2010induced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation. Mechanistically, cigarette smoke (CS) exposure upregulated AARS1 levels in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Elevated AARS1 catalyzed the transfer of a lactyl group to RUNX3 at the K193 site, leading to the elevation of lactylation of RUNX3\u2010K193, and inhibited RUNX3 fusion with autophagosomes for degradation. Subsequent accumulation of RUNX3 promoted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation and enhanced their cytotoxicity. Here we demonstrate, using a CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2010lung organoid co\u2010culture model and an experimental emphysema model induced by CS, that treatment with the lactate inhibitor DCA and silencing of AARS1 abrogated CS\u2010induced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation, which ameliorated emphysematous pathological changes in mouse lung tissue. Moreover, elevated lactate and AARS1 negatively correlated with lung function in human populations. Collectively, this study reveals that AARS1 drives CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation by mediating RUNX3 lactylation to inhibit its autolysosomal degradation, and targeting of AARS1 may provide new insights into the therapy of emphysema.\n                  <\/jats:p>","DOI":"10.1002\/advs.76949","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:37:45Z","timestamp":1786009065000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AARS1\u2010Mediated RUNX3 K193 Lactylation Enhances the Activation and Cytotoxicity of CD8\n                    <sup>+<\/sup>\n                    T Cells in Smoking\u2010Related Emphysema"],"prefix":"10.1002","author":[{"given":"Ying","family":"Zhu","sequence":"first","affiliation":[{"name":"Center For Global Health The Key Laboratory of Modern Toxicology Ministry of Education School of Public Health Suzhou Institute for Advanced Study of Public Health Gusu School Nanjing Medical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Center For Global Health The Key Laboratory of Modern Toxicology Ministry of Education School of Public Health Suzhou Institute for Advanced Study of Public Health Gusu School Nanjing Medical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Wuxi People's Hospital of Nanjing Medical University Wuxi Medical Center Nanjing Medical University  Wuxi Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoqiao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Wuxi People's Hospital of Nanjing Medical University Wuxi Medical Center Nanjing Medical University  Wuxi Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Nanjing Medical University  Suzhou Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Center For Global Health The Key Laboratory of Modern Toxicology Ministry of Education School of Public Health Suzhou Institute for Advanced Study of Public Health Gusu School Nanjing Medical University  Nanjing Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Nanjing Medical University  Suzhou Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Nanjing Medical University  Suzhou Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Wuxi People's Hospital of Nanjing Medical University Wuxi Medical Center Nanjing Medical University  Wuxi Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2767-9297","authenticated-orcid":false,"given":"Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The Affiliated Wuxi People's Hospital of Nanjing Medical University Wuxi Medical Center Nanjing Medical University  Wuxi Jiangsu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Animal Core Facility Jiangsu Animal Experimental Center of Medical &amp; Pharmaceutical Research Nanjing Medical University  Nanjing Jiangsu People's Republic of 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