Cigarette smoke has opposite effects in murine models of ulcerative colitis and Crohn’s disease through mucosal immunity and gut environment

• Published in: The Journal of immunology (1950) Vol. 204; no. 1_Supplement; pp. 233 - 233.19
• Main Authors: Kitabatake, Masahiro, Nishioka, Tatsuki, Ouji-Sageshima, Noriko, Ito, Toshihiro
• Format: Journal Article
• Language: English
• Published: 01.05.2020
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.204.Supp.233.19

Abstract Inflammatory bowel diseases (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), represent chronic intestinal inflammation, and the exact cause of each disease is still unclear. Clinical studies have reported that smoking exacerbates pathogenesis in CD patients, whereas it plays a protective factor in UC patients. However, the mechanism of how smoking has different effects on UC and CD remains unknown. In this study, C57BL/6 mice were exposed with cigarette smoke (CS; 20 cigarettes/day) for two weeks, and then, mice were administered dextran sodium sulfate (DSS) or tri-nitrobenzene sulfonic acid (TNBS) to induce colitis as UC and CD model, respectively. CS exposure improved the colon inflammation and histological score in UC model, while it worsened them in CD model. In UC model, CS induced regulatory T cells (Tregs) and decreased activated CD8+ T cells. Diversity of gut microbiota was expanded by CS exposure. Interestingly, proportion of Lachnospiraceae, which is thought to generate short chain fatty acid and induce Tregs, was increased. On the other hand, Th1 cells were significantly increased in lamina propria in CD model, and diversity of gut microbiota was decreased and proportion of Enterobacteriaceae, which is considered to associate with onset and enhanced inflammation in IBD, was remarkably increased in CD model. Moreover, one of metabolites induced by CS in UC model improved DSS-induced colitis by increasing Tregs and by decreasing inflammatory cytokines in colon. These results suggest that CS exposure regulates pathogenesis of IBD by changing gut environment including gut microbiota as well as intestinal immunity.