{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:47:33Z","timestamp":1785433653571,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370031"],"award-info":[{"award-number":["82370031"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82370031"],"award-info":[{"award-number":["82370031"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018806","name":"Science and Technology Department of Hubei Province","doi-asserted-by":"publisher","award":["2025AFB792"],"award-info":[{"award-number":["2025AFB792"]}],"id":[{"id":"10.13039\/501100018806","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2025AFB792"],"award-info":[{"award-number":["2025AFB792"]}],"id":[{"id":"https:\/\/ror.org\/00tbh0t11","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Allergic asthma is associated with a reduction in the number of regulatory T cells (Tregs). Although interleukin-27 (IL-27) has been shown to modulate Tregs potentially through the Lymphocyte-activation gene 3 (Lag3) pathway, the underlying mechanism remains incompletely defined. Objective: This study sought to determine whether IL-27 ameliorates airway inflammation in asthma by modulating Tregs in a Lag3-dependent manner. Acute asthma was induced in wild-type (WT) and Lag3 knockout (Lag3\u2212\/\u2212) mice through sensitization and challenge with house dust mite (HDM). A treatment group received intranasal recombinant IL-27 prior to challenges. In WT mice, IL-27 administration significantly attenuated airway inflammation, goblet cell hyperplasia, and total cell counts in bronchoalveolar lavage fluid (BALF), along with reduced levels of Th2 cytokines (IL-4, IL-5). It also upregulated T-bet (Th1) mRNA expression, downregulated GATA-3 (Th2) and ROR\u03b3t (Th17) levels, and increased the proportions of CD4+ Foxp3+ Tregs, CTLA4+ Tregs, and Lag3+ Tregs in lung tissue. Conversely, in Lag3\u2212\/\u2212 mice, the protective effects of IL-27 were completely abrogated, with no observed increases in Treg populations or suppression of Th2\/Th17 immune responses. The anti-asthmatic effect of exogenous IL-27 is associated with increased Treg frequency and upregulation of inhibitory markers, with Lag3 serving as a pivotal target on Tregs.<\/jats:p>","DOI":"10.3390\/ijms27146260","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T03:06:52Z","timestamp":1784084812000},"page":"6260","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-27-Dependent Lag3 Regulates CD4+ Foxp3+ Regulatory T Cells to Alleviate Airway Inflammation in Allergic Asthma"],"prefix":"10.3390","volume":"27","author":[{"given":"Miaojuan","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3926-8923","authenticated-orcid":false,"given":"Rongyao","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0324-0013","authenticated-orcid":false,"given":"Jiong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxiang","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.cell.2021.02.016","article-title":"The basic immunology of asthma","volume":"184","author":"Hammad","year":"2021","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.immuni.2023.01.004","article-title":"Principles of regulatory T cell function","volume":"56","author":"Dikiy","year":"2023","journal-title":"Immunity"},{"key":"ref_3","first-page":"4158","article-title":"Foxp3+ Treg\/Th17 cell imbalance in lung tissues of mice with asthma","volume":"8","author":"Jiang","year":"2015","journal-title":"Int. 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