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Here, we focused on investigating the molecular and cellular effects of alcohol ingestion on lung immunity in male and female subjects using population-based human lung transcriptomics analysis and an experimental mouse model of chronic alcohol drinking using the National Institute on Alcohol Abuse and Alcoholism alcohol feeding model. Flow cytometry and transcriptomics analyses in lungs revealed a sexually dimorphic effect of chronic alcohol drinking on lung immunity in both human and mouse. Male lungs were more sensitive to chronic alcohol drinking\u2013induced dysregulation of lung immunity compared with female lungs. Furthermore, comparative transcriptomics analysis using lungs and liver samples from matched human and mouse subjects demonstrated that lungs were more sensitive than liver to the effects of alcohol in downregulating immune-related genes and pathways. Furthermore, the transcriptomics analysis provided evidence that immunometabolic change is a central driver in lung alteration by downregulating the immune pathways and upregulating metabolic pathways. Chronic alcohol consumption resulted in reduced mTOR signaling and decreased immune cell populations. The mTOR signaling axis may serve as an upstream regulator of alcohol-induced dysregulation in lung immunity.<\/jats:p>","DOI":"10.1165\/rcmb.2024-0086oc","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T16:07:30Z","timestamp":1721318850000},"page":"559-576","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":5,"title":["Chronic Alcohol Intake Compromises Lung Immunity by Altering Immunometabolism in Humans and Mouse Models"],"prefix":"10.1093","volume":"71","author":[{"given":"Lenny","family":"Pommerolle","sequence":"first","affiliation":[{"name":"Section on Fibrotic Disorders"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Arif","sequence":"additional","affiliation":[{"name":"Section on Fibrotic Disorders"},{"name":"Laboratory of Cardiovascular Physiology and Tissue Injury, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Behee","sequence":"additional","affiliation":[{"name":"Section on Fibrotic Disorders"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corynn N.","family":"Appolonia","sequence":"additional","affiliation":[{"name":"Section on Fibrotic Disorders"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Basu","sequence":"additional","affiliation":[{"name":"Section on Fibrotic Disorders"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaelin M.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Section on Fibrotic Disorders"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles N.","family":"Zawatsky","sequence":"additional","affiliation":[{"name":"Section on Fibrotic Disorders"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Johnson","sequence":"additional","affiliation":[{"name":"Section on Fibrotic Disorders"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Rivellini","sequence":"additional","affiliation":[{"name":"Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua K.","family":"Park","sequence":"additional","affiliation":[{"name":"Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8597-7253","authenticated-orcid":false,"given":"Resat","family":"Cinar","sequence":"additional","affiliation":[{"name":"Section on Fibrotic Disorders"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"2026012204182821300_bib1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.35946\/arcr.v38.2.07","article-title":"Alcohol and the lung","volume":"38","author":"Mehta","year":"2017","journal-title":"Alcohol Res"},{"key":"2026012204182821300_bib2","doi-asserted-by":"crossref","first-page":"L813","DOI":"10.1152\/ajplung.00348.2006","article-title":"The alcoholic lung: epidemiology, pathophysiology, and potential therapies","volume":"292","author":"Joshi","year":"2007","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026012204182821300_bib3","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1111\/j.1530-0277.2009.01005.x","article-title":"Alcohol abuse enhances pulmonary edema in acute respiratory distress syndrome","volume":"33","author":"Berkowitz","year":"2009","journal-title":"Alcohol Clin Exp Res"},{"key":"2026012204182821300_bib4","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.3390\/ijerph15061083","article-title":"Alcoholism: a multi-systemic cellular insult to organs","volume":"15","author":"Dguzeh","year":"2018","journal-title":"Int J Environ Res Public Health"},{"key":"2026012204182821300_bib5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.alcohol.2023.04.002","article-title":"Alcohol and immunology: mechanisms of multi-organ damage. 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