title: Cigarette smoking alters epithelial apoptosis and immune composition in murine GALT.
abstract: 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.
authors.affiliation: Department of Pathology, Ghent University, Belgium. Stephanie.Verschuere@ugent.be
authors.forename: Stephanie
authors.initials: S
authors.lastname: Verschuere
authors.forename: Ken R
authors.initials: KR
authors.lastname: Bracke
authors.forename: Tine
authors.initials: T
authors.lastname: Demoor
authors.forename: Maud
authors.initials: M
authors.lastname: Plantinga
authors.forename: Phebe
authors.initials: P
authors.lastname: Verbrugghe
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Ferdinande
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.forename: Guy G G
authors.initials: GG
authors.lastname: Brusselle
authors.forename: Claude A
authors.initials: CA
authors.lastname: Cuvelier
mesh_terms: D000818:Animals; D017209:Apoptosis; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000276:immunology / Q000473:pathology*; D014026:Nicotiana
chemical_list: D016753:Interleukin-10