{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T01:16:53Z","timestamp":1791076613200,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>IFN-\u03b3+CD4+ cells (type 1 helper T cells, Th1) represent a critical component of the inflammatory environment in the lungs of chronic obstructive pulmonary disease (COPD). Identifying influencing factors related to COPD-associated Th1 cells will enhance our understanding of the inflammatory mechanisms involved and facilitate the development of targeted interventions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We describe T-cell immunoglobulin and mucin-domain containing-3 (Tim3) as a key gene regulating COPD-associated Th1 cells through single-cell sequencing, flow cytometry and knockout mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings indicate that Havcr2 expression gradually increases during CD4+ T cell activation in COPD mice, with Tim3 being highly expressed on both CD4+ T cells and Th1 cells. Notably, the knockout of HAVCR2 further promotes the infiltration of CD4+ T cells and the expression of IFN-\u03b3 in the lungs, resulting in a more severe emphysema phenotype, although it does not significantly affect TNF-\u03b1 expression. Additionally, NFIL3, an upstream regulator of Tim3, is also highly expressed in the CD4+ T cells of COPD mice. Mice with NFIL3 knockout exhibit phenotypes similar to those of HAVCR2 knockout mice, along with a significant downregulation of Tim3 expression. <jats:italic>In vitro<\/jats:italic>, we simulated the activation process by polarizing primary CD4+ Tn cells from COPD mice and observed that NFIL3\/Tim3 expression was significantly upregulated following Th1 polarization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrates that the NFIL3\/Tim3 axis plays a role in Th1 imbalance in the lungs of COPD by inhibiting Th1 differentiation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1482213","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T04:44:30Z","timestamp":1730436270000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["NFIL3\/Tim3 axis regulates effector Th1 inflammation in COPD 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