LAUSR

OBJECTIVE Smoking is associated with numerous inflammatory and autoimmune conditions. The goal of this study was to examine whether increased expression of G-protein-coupled receptor 15 (GPR15) on helper T cells in smokers could predispose to these conditions through its relationship with inflammatory biomarkers. METHODS We used flow cytometric measurement of GPR15+CD3+CD4+ helper T cells and serum assays for C-reactive protein (CRP) and 17 cytokines drawn from peripheral blood samples from a cohort of n = 62 primarily African American young adults (aged 27-35 years). These variables were examined cross-sectionally in conjunction with serum biomarkers of tobacco (cotinine) and cannabis (tetrahydrocannabinol) use and lifestyle factors potentially impacting immune function in correlational analyses and linear regression models. RESULTS Tobacco and cannabis smoking were strongly associated with increased GPR15 expression on helper T cells (p < 0.001), which was in turn was strongly associated with the ratio of pro-inflammatory to anti-inflammatory cytokines (p < 0.001). Mediation analyses indicated increased GPR15 expression accounted for roughly half of the relationship between smoking variables and pro-inflammatory to anti-inflammatory cytokine balance. CRP was not associated with cannabis or tobacco use or GPR15+ expression, but was associated with body mass index (p < 0.001). These relationships persisted after controlling for lifestyle and medical factors impacting immune function. CONCLUSIONS Increased expression of GPR15 by helper T cells in smokers may mediate some of the relationship between smoking and a pro-inflammatory cytokine milieu. Better understanding of this relationship may help uncover how smoking increases the risk of inflammatory diseases.