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Opposing Effects of Smoking in Ulcerative Colitis and Crohn's Disease May Be Explained by Differential Effects on Dendritic Cells

Ueno, Aito PhD*; Jijon, Humberto MD, PhD*,†; Traves, Suzanne PhD; Chan, Ronald MSc*; Ford, Kim BPE*; Beck, Paul L. MD, PhD*,†; Iacucci, Marietta MD, PhD; Fort Gasia, Miriam MD*,†; Barkema, Herman W. DVM, PhD*; Panaccione, Remo MD*,†; Kaplan, Gilaad G. MD, MPh*,†; Proud, David PhD; Ghosh, Subrata MD*,†

doi: 10.1097/MIB.0000000000000018
Original Basic Science Articles

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.

Article first published online 31 March 2014Supplemental Digital Content is Available in the Text.

*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.

Reprints: Aito Ueno, PhD, Alberta IBD Consortium/Gastrointestinal Research Group, Snyder Institute for Chronic Diseases, University of Calgary, 2500 University Dr. NW, Calgary, AB, T2N1N4, Canada (e-mail:

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Alberta IBD Consortium was supported by Alberta Innovates-Health Solutions.

Presented at the Digestive Disease Week Conference (Sa1774), Chicago, IL, in May 2011 and the abstract published in Gastroenterology. 2011;144(suppl 1):S303.

The authors have no conflicts of interest to disclose.

Received January 01, 2014

Accepted January 30, 2014

© Crohn's & Colitis Foundation of America, Inc.
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