{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:29:52Z","timestamp":1783531792463,"version":"3.55.0"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260011"],"award-info":[{"award-number":["82260011"]}],"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":["81860009"],"award-info":[{"award-number":["81860009"]}],"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":["81800037"],"award-info":[{"award-number":["81800037"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011827","name":"Guangxi Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011827","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"Abstract<\/jats:title>Overexpression of T\u2010cell immunoglobulin and mucin\u2010domain containing\u20103 (TIM<\/jats:styled-content>\u20103) on T cells has been observed in smokers. However, whether and how galectin\u20109 (Gal\u20109)\/TIM<\/jats:styled-content>\u20103 signal between T\u2010regulatory cells (Tregs) and type 17 helper (Th17) cells contributes to tobacco smoke\u2010induced airway inflammation remains unclear. Here, we aimed to explore the role of the Gal\u20109\/TIM<\/jats:styled-content>\u20103 signal between Tregs and Th17 cells during chronic tobacco smoke exposure. Tregs phenotype and the expression of TIM<\/jats:styled-content>\u20103 on CD4<\/jats:styled-content>+<\/jats:sup> T cells were detected in a mouse model of experimental emphysema. The role of TIM<\/jats:styled-content>\u20103 in CD4<\/jats:styled-content>+<\/jats:sup> T cells was explored in a HAVCR2<\/jats:styled-content>\u2212\/\u2212<\/jats:sup> mouse model and in mice that received recombinant anti\u2010TIM3<\/jats:styled-content>. The crosstalk between Gal\u20109 and Tim\u20103 was evaluated by coculture Tregs with effector CD4<\/jats:styled-content>+<\/jats:sup> T cells. We also invested the expression of Gal\u20109 in Tregs in patients with COPD<\/jats:styled-content>. Our study revealed that chronic tobacco smoke exposure significantly reduces the frequency of Tregs in the lungs of mice and remarkably shapes the heterogeneity of Tregs by downregulating the expression of Gal\u20109. We observed a pro\u2010inflammatory but restrained phenotypic transition of CD4<\/jats:styled-content>+<\/jats:sup> T cells after tobacco smoke exposure, which was maintained by TIM<\/jats:styled-content>\u20103. The restrained phenotype of CD4<\/jats:styled-content>+<\/jats:sup> T cells was perturbed when TIM<\/jats:styled-content>\u20103 was deleted or neutralised. Tregs from the lungs of mice with emphysema displayed a blunt ability to inhibit the differentiation and proliferation of Th17 cells. The inhibitory function of Tregs was partially restored by using recombinant Gal\u20109. The interaction between Gal\u20109 and TIM<\/jats:styled-content>\u20103 inhibits the differentiation of Th17 cells and promotes apoptosis of CD4<\/jats:styled-content>+<\/jats:sup> T cells, possibly by interfering with the expression of retinoic acid receptor\u2010related orphan receptor gamma t. The expression of Gal\u20109 in Tregs was reduced in patients with COPD<\/jats:styled-content>, which was associated with Th17 response and lung function. These findings present a new paradigm that impairment of Gal\u20109\/Tim\u20103 crosstalk between Tregs and Th17 cells during chronic tobacco smoke exposure promotes tobacco smoke\u2010induced airway\/lung inflammation.<\/jats:p>","DOI":"10.1111\/imm.13820","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T12:30:23Z","timestamp":1717417823000},"page":"152-171","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Impairment of Gal\u20109 and Tim\u20103 crosstalk between Tregs and Th17 cells drives tobacco smoke\u2010induced airway inflammation"],"prefix":"10.1111","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1377-7818","authenticated-orcid":false,"given":"Shilin","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine the First Affiliated Hospital of Guangxi Medical University Nanning Guangxi 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First Affiliated Hospital of Guangxi Medical University Nanning Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitao","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine the First Affiliated Hospital of Guangxi Medical University Nanning Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine the First Affiliated Hospital of Guangxi Medical University Nanning Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Wuming Hospital of Guangxi Medical University Nanning Guangxi 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