title: Colonic inflammation in mice is improved by cigarette smoke through iNKT cells recruitment.
abstract: Cigarette smoke (CS) protects against intestinal inflammation during ulcerative colitis. Immunoregulatory mechanisms sustaining this effect remain unknown. The aim of this study was to assess the effects of CS on experimental colitis and to characterize the intestinal inflammatory response at the cellular and molecular levels. Using the InExpose® System, a smoking device accurately reproducing human smoking habit, we pre-exposed C57BL/6 mice for 2 weeks to CS, and then we induced colitis by administration of dextran sodium sulfate (DSS). This system allowed us to demonstrate that CS exposure improved colonic inflammation (significant decrease in clinical score, body weight loss and weight/length colonic ratio). This improvement was associated with a significant decrease in colonic proinflammatory Th1/Th17 cytokine expression, as compared to unexposed mice (TNF (p=0.0169), IFNγ (p<0.0001), and IL-17 (p=0.0008)). Smoke exposure also induced an increased expression of IL-10 mRNA (p=0.0035) and a marked recruitment of iNKT (invariant Natural Killer T; CD45+ TCRβ+ CD1d tetramer+) cells in the colon of DSS-untreated mice. Demonstration of the role of iNKT cells in CS-dependent colitis improvement was performed using two different strains of NKT cells deficient mice. Indeed, in Jα18KO and CD1dKO animals, CS exposure failed to induce significant regulation of DSS-induced colitis both at the clinical and molecular levels. Thus, our study demonstrates that iNKT cells are pivotal actors in the CS-dependent protection of the colon. These results highlight the role of intestinal iNKT lymphocytes and their responsiveness to environmental stimuli. Targeting iNKT cells would represent a new therapeutic way for inflammatory bowel diseases.
authors: Université Lille Nord de France, Lille, France.
authors: Muriel
authors: M
authors: Montbarbon
authors: Muriel
authors: M
authors: Pichavant
authors: Audrey
authors: A
authors: Langlois
authors: Edmone
authors: E
authors: Erdual
authors: François
authors: F
authors: Maggiotto
authors: Christel
authors: C
authors: Neut
authors: Thierry
authors: T
authors: Mallevaey
authors: Sébastien
authors: S
authors: Dharancy
authors: Laurent
authors: L
authors: Dubuquoy
authors: François
authors: F
authors: Trottein
authors: Antoine
authors: A
authors: Cortot
authors: Pierre
authors: P
authors: Desreumaux
authors: Philippe
authors: P
authors: Gosset
authors: Benjamin
authors: B
authors: Bertin
mesh_terms: D000818:Animals; D002452:Cell Count; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D012906:Smoke; D014026:Nicotiana / Q000737:chemistry*
chemical_list: D016207:Cytokines; D012906:Smoke; D016264:Dextran Sulfate
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