Journal
LABORATORY INVESTIGATION
Volume 91, Issue 7, Pages 1056-1067Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.2011.74
Keywords
apoptosis; cigarette smoke; Crohn's disease; dendritic cell; intestinal epithelium; Peyer's patch
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Funding
- Ghent University [01J17507, BOF 10/GOA/021, 01D21009]
- Fund for Scientific Research (FWO) in Flanders
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Smokers have a twofold increased risk to develop Crohn's disease (CD). However, little is known about the mechanisms through which smoking affects CD pathogenesis. Especially Crohn's ileitis is negatively influenced by smoking. Interestingly, the ileum and, more in particular, the Peyer's patches in the terminal ileum are also the sites where the first CD lesions are found. Several chemokines are implicated in the pathogenesis, among which is the CCL20-CCR6 pathway. Here, we studied the gut-associated lymphoid tissue in C57BL/6 wild-type mice and in CCR6-deficient mice after exposure to air or cigarette smoke for 24 weeks. Apoptotic index of the follicle-associated epithelium overlying the Peyer's patches was evaluated. We found that chronic smoke exposure induced apoptosis in the follicle-associated epithelium. Furthermore, immune cell numbers and differentiation along with chemokine expression were determined in Peyer's patches. Important changes in immune cell composition were observed: total dendritic cells, CD4+ T cells (including regulatory T cells) and CD8+ T cells increased significantly after smoke exposure. The CD11b+ dendritic cell subset almost doubled. Interestingly, these changes were accompanied by an upregulated mRNA expression of the chemokines CCL9 and CCL20. However, no differences in the increase of dendritic cells were observed between wild-type and CCR6-deficient mice. Our results show that cigarette smoke exposure increases apoptosis in the follicle-associated epithelium and is associated with immune cell accumulation in Peyer's patches. Laboratory Investigation (2011) 91, 1056-1067; doi:10.1038/labinvest.2011.74; published online 2 May 2011
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