Lenny Pommerolle, Muhammad Arif, Madeline Behee, Corynn Appolonia, Abhishek Basu, Kaelin M Wolf, Charles N Zawatsky, Natalie Johnson, Olivia Rivellini, Joshua K Park, Resat Cinar
{"title":"Chronic Alcohol Intake Compromises Lung Immunity by Altering Immunometabolism in Humans and Mouse Models.","authors":"Lenny Pommerolle, Muhammad Arif, Madeline Behee, Corynn Appolonia, Abhishek Basu, Kaelin M Wolf, Charles N Zawatsky, Natalie Johnson, Olivia Rivellini, Joshua K Park, Resat Cinar","doi":"10.1165/rcmb.2024-0086OC","DOIUrl":null,"url":null,"abstract":"<p><p>Chronic alcohol consumption disrupts lung immunity and host defense mechanisms, rendering individuals with alcohol use disorder more susceptible to developing inflammatory lung conditions with poor prognoses. 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 NIAAA alcohol feeding model. Flow cytometry and transcriptomics analyses in lungs revealed a sexually dimorphic effect of chronic alcohol drinking on lung immunity of both human and mouse. The male lungs were more sensitive to chronic alcohol drinking-induced dysregulation of lung immunity compared to the females. Furthermore, comparative transcriptomics analysis using lungs and liver samples from matched human and mouse subjects exhibited that lungs were more sensitive than the liver to the effects of alcohol in down-regulating 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. mTOR signaling axis may serve as an upstream regulator of alcohol-induced dysregulation in lung immunity.</p>","PeriodicalId":7655,"journal":{"name":"American Journal of Respiratory Cell and Molecular Biology","volume":null,"pages":null},"PeriodicalIF":5.9000,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Respiratory Cell and Molecular Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1165/rcmb.2024-0086OC","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Chronic alcohol consumption disrupts lung immunity and host defense mechanisms, rendering individuals with alcohol use disorder more susceptible to developing inflammatory lung conditions with poor prognoses. 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 NIAAA alcohol feeding model. Flow cytometry and transcriptomics analyses in lungs revealed a sexually dimorphic effect of chronic alcohol drinking on lung immunity of both human and mouse. The male lungs were more sensitive to chronic alcohol drinking-induced dysregulation of lung immunity compared to the females. Furthermore, comparative transcriptomics analysis using lungs and liver samples from matched human and mouse subjects exhibited that lungs were more sensitive than the liver to the effects of alcohol in down-regulating 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. mTOR signaling axis may serve as an upstream regulator of alcohol-induced dysregulation in lung immunity.
期刊介绍:
The American Journal of Respiratory Cell and Molecular Biology publishes papers that report significant and original observations in the area of pulmonary biology. The focus of the Journal includes, but is not limited to, cellular, biochemical, molecular, developmental, genetic, and immunologic studies of lung cells and molecules.