{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T03:40:10Z","timestamp":1758858010401,"version":"3.44.0"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG067457"],"award-info":[{"award-number":["R01 AG067457"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["75N92019D00031"],"award-info":[{"award-number":["75N92019D00031"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alcohol consumption affects immune function, with excessive intake linked to immune suppression and inflammation. However, its impact on immune cell phenotypes remains unclear. This study investigates the association between alcohol consumption and immune cell profiles in a well\u2010characterized Framingham Heart Study (FHS) cohort while examining sex\u2010specific differences in alcohol\u2010immune cell associations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed data from 996 participants of the FHS Offspring cohort who underwent immune cell phenotyping and completed an alcohol questionnaire during Exam 7 (1998\u20132001). Alcohol intake was categorized as abstainer, moderate, at\u2010risk, or heavy drinking. Linear mixed\u2010effects models examined associations between alcohol intake and 15 immune cell phenotypes, adjusting for age, sex, and Cytomegalovirus (CMV) (Model 1) and additional covariates (Model 2). False discovery rate (FDR) correction was applied for multiple testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CD4+ Tn\/Tm ratio showed a significant nonlinear relationship with alcohol categories in Model 1 (<jats:italic>p<\/jats:italic>\u2009=\u20090.002, FDR\u2009=\u20090.03), with higher ratios in moderate (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.26) and at\u2010risk drinkers (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.26) compared with abstainers; effects were smaller in Model 2 (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.23 and <jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.23, respectively). Sex\u2010stratified analyses revealed that among males, alcohol consumption was associated with several immune cell phenotypes in Model 1, and with CD8+ Tn\/Tm ratio in Model 2 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0001, FDR\u2009=\u20090.002), where moderate drinking was associated with higher CD8+ Tn\/Tm ratio compared with abstainers (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.29). Among male drinkers, consumption level was also associated with CD8+ Tn\/Tm ratio in both models: at\u2010risk and heavy consumption showed significantly lower CD8+ Tn\/Tm ratio compared with moderate drinkers (<jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.43 and <jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.46, respectively, in Model 2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Alcohol consumption exhibits a nonlinear relationship with certain immune cells, with moderate intake potentially benefiting immunity, while higher consumption may compromise immune homeostasis. Given the study's cross\u2010sectional design, causality cannot be inferred; nonetheless, our sex\u2010specific, dose\u2010dependent findings merit confirmation in longitudinal cohorts.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.70122","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T11:20:13Z","timestamp":1753788013000},"page":"1953-1961","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alcohol consumption and immune cell profiles: Insights from the Framingham Heart Study"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0291-0485","authenticated-orcid":false,"given":"Ahmed A. 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