免疫
肺
医学
免疫学
酒
生物
生理学
内科学
免疫系统
生物化学
作者
Lenny Pommerolle,Muhammad Arif,Madeline Behee,Corynn Appolonia,Abhishek Basu,Kaelin M. Wolf,Charles N. Zawatsky,Natalie Johnson,Olivia Rivellini,Joshua K. Park,Reşat Çınar
标识
DOI:10.1165/rcmb.2024-0086oc
摘要
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.
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