Opposing effects of smoking in ulcerative colitis and Crohn's disease may be explained by differential effects on dendritic cells

Research output: Contribution to journalArticlepeer-review

Authors

  • Aito Ueno
  • Humberto Jijon
  • Suzanne Traves
  • Ronald Chan
  • Kim Ford
  • Paul L Beck
  • Miriam Fort Gasia
  • Herman W Barkema
  • Remo Panaccione
  • Gilaad G Kaplan
  • David Proud

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)800-10
Number of pages11
JournalInflammatory Bowel Diseases
Volume20
Issue number5
Early online date31 Mar 2014
Publication statusPublished - 1 May 2014

Keywords

  • Adult, CD4-Positive T-Lymphocytes, Case-Control Studies, Cell Differentiation, Chemokines, Colitis, Ulcerative, Crohn Disease, Cytokines, Dendritic Cells, Female, Flow Cytometry, Follow-Up Studies, Granulocyte-Macrophage Colony-Stimulating Factor, Humans, Interleukin-4, Male, Monocytes, Prognosis, Smoking, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, smoking in IBD, dendritic cells in IBD, environmental risk, adaptive immune system, T cells and regulatory T cells