title: Opposing effects of smoking in ulcerative colitis and Crohn's disease may be explained by differential effects on dendritic cells.
abstract: BACKGROUND
  The mechanisms underlying the differential effects of cigarette smoking in patients with Crohn's disease (CD) and ulcerative colitis (UC) remain unknown. Smoking has been demonstrated to be protective in UC, whereas in CD it has been shown to be associated with a more severe course, more frequent relapses, and postoperative recurrence. Dendritic cells (DC) play a critical role in T-cell activation and differentiation. Thus, we examined the effects of in vitro exposure to cigarette smoke extract (CSE) on phenotype/function of DC obtained from patients with UC and CD.
  
  
  METHODS
  Sixty-eight subjects were recruited including 30 patients with CD, 19 patients with UC, and 19 healthy controls. Peripheral blood monocytes were differentiated to DC in presence of IL-4 and granulocyte-macrophage colony-stimulating factor. The influence of CSE on Mo-DC subsets, cytokine expression, and ability to drive T cell proliferation and polarization were examined.
  
  
  RESULTS
  CSE affected DC phenotypes including increases in class-2 major histocompatibility complex and costimulatory molecules and decreases in CXCL10 and CCL3 levels in UC compared with CD samples. Furthermore, CSE also altered DC function resulting in increasing T cell proliferation and Th1 polarization in CD, whereas it increased Foxp3+ T cells and decreased the Th1 subset in UC samples.
  
  
  CONCLUSIONS
  CSE modulates DC phenotype and function in patients with UC leading to increased prevalence of Foxp3+ CD4 T cells, whereas in patients with CD it skews toward Th1 subsets. Differential DC responses to CSE between CD and UC may contribute to the differential effects associated with cigarette smoking status.
authors.affiliation: *Alberta IBD Consortium/Gastrointestinal Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada; †Department of Medicine and IBD Clinic, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada; and ‡Department of Physiology and Pharmacology, Airway Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada.
authors.forename: Aito
authors.initials: A
authors.lastname: Ueno
authors.forename: Humberto
authors.initials: H
authors.lastname: Jijon
authors.forename: Suzanne
authors.initials: S
authors.lastname: Traves
authors.forename: Ronald
authors.initials: R
authors.lastname: Chan
authors.forename: Kim
authors.initials: K
authors.lastname: Ford
authors.forename: Paul L
authors.initials: PL
authors.lastname: Beck
authors.forename: Marietta
authors.initials: M
authors.lastname: Iacucci
authors.forename: Miriam
authors.initials: M
authors.lastname: Fort Gasia
authors.forename: Herman W
authors.initials: HW
authors.lastname: Barkema
authors.forename: Remo
authors.initials: R
authors.lastname: Panaccione
authors.forename: Gilaad G
authors.initials: GG
authors.lastname: Kaplan
authors.forename: David
authors.initials: D
authors.lastname: Proud
authors.forename: Subrata
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D018925:Chemokines / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000503:physiopathology*; D003424:Crohn Disease / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006801:Humans; D015847:Interleukin-4 / Q000008:administration & dosage; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D012907:Smoking / Q000009:adverse effects*
chemical_list: D018925:Chemokines; D016207:Cytokines; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor