Inflammatory biomarker relationships with helper T cell GPR15 expression and cannabis and tobacco smoking

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 antiinflammatory 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.