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However, the complex roles of functionally heterogeneous Treg subsets in the lung during the resolution of acute inflammation remain unclear. To investigate the role of peripherally induced Tregs, we utilized mice lacking conserved noncoding sequence 1 (CNS1) of the Foxp3 locus, a genetic deletion that impairs peripheral Treg induction. We found that CNS1-deficient mice exhibit greater mortality and delayed resolution during ALI. Tregs induced via CNS1 modulated antiviral and proinflammatory immune responses in the lung during influenza. Mechanistically, single-cell RNA sequencing reveals that CNS1-deficient Tregs fail to fully engage the Treg transcriptional program that supports optimal suppressive and reparative function in the lung. Our findings highlight a critical role for CNS1-dependent peripherally induced Tregs in determining ALI severity, providing insight into how distinct Treg subpopulations may be therapeutically harnessed to mitigate tissue damage during respiratory disease.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag119","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:56:31Z","timestamp":1779897391000},"source":"Crossref","is-referenced-by-count":0,"title":["CNS1-dependent regulatory T cells shape recovery from acute lung injury"],"prefix":"10.1093","volume":"215","author":[{"given":"Morgan J","family":"McCullough","sequence":"first","affiliation":[{"name":"Marsico Lung Institute, UNC School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]},{"name":"Department of Microbiology and Immunology, UNC School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United 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G","family":"Vincent","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, UNC School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]},{"name":"Lineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]},{"name":"Division of Hematology, UNC School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Justin","family":"Milner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, UNC School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]},{"name":"Lineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United 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Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire M","family":"Doerschuk","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute, UNC School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]},{"name":"Department of Microbiology and Immunology, UNC School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]},{"name":"Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, UNC School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]},{"name":"Department of Pathology and Laboratory Medicine, UNC School of Medicine, University of North Carolina at Chapel Hill , Chapel Hill, NC,","place":["United States"]},{"name":"Center for Airways Disease, UNC School of Medicine, University 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