SMOKING-INDUCED MUCOSAL INFLAMMATION IS NEGATIVELY REGULATED by the INTERPLAY between IL-10, IL-17 and the GUT MICROBIOTA

Cigarette smoking remains the major environmental risk factor for Crohn’s disease and Chronic Obstructive Pulmonary disease through unknown regulatory mechanisms. Herein, we demonstrate that chronic exposure to cigarette smoke enhanced IL-10 production. Importantly, Il-10 deficiency triggered mucosal immune deviation toward Th1 and Th17-type responses to cigarette smoking. Vancomycin, but not colistin, prophylaxis reversed smoking-induced lung function decline and restricted pathogenic Th17 response in the ileum and the lung. Collectively, we identified a gene-plus-tobacco interaction that restricts mucosal immune deviation toward pathogenic Th17 inflammatory response to Gram positive bacteria. We propose that the mutualistic interplay of Il-10 and the gut microbiota intrinsically controls T cell mutualism in the lung and the intestine. Tobacco smoking may predispose to chronic intestinal inflammation in patients with IL10 defects or a failure to efficiently activate Treg cells.