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 þ T cells (including regulatory T cells) and CD8 þ T cells increased significantly after smoke exposure. The CD11b þ 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.

Epigenetic biomarkers of T-cells in human glioma

“…There is strong evidence that cigarette smoke exposure leads to the accumulation of Tregs in respiratory airways in mice 34 and humans 35 as well as in the gut epithelium of exposed mice. 36 Elevated blood Treg numbers may reflect the mobilization and trafficking of Tregs into cigarette smoke exposed tissues. This is biologically plausible given the fact that cigarette smoking is associated with increases in the expression of the Treg chemoattractants CCL2 and CCL22.…”

Transient Receptor Potential Channels in Intestinal Inflammation: What Is the Impact of Cigarette Smoking?

“…In a mouse model, we have demonstrated that, similarly to the lung, CS affects the gut immune system by enhancing the recruitment of CD11b+ DCs, CD4+ and CD8+ T cells to the mouse ileal Peyer's patches, which are the main lymphoid organs in the gut [142]. Furthermore, CS alters the production of immune factors in the mouse ileum (increased CXCL2, an IL-8 homolog) and in the proximal colon (increased IL-6) [138].…”

Cigarette smoke and the terminal ileum: increased autophagy in murine follicle-associated epithelium and Peyer’s patches

“…We recently demonstrated that chronic CS exposure induces apoptosis in the FAE. We suggested that this is due to oxidative stress associated with smoking (Verschuere et al 2011). In the present study, we examined the presence of autophagic vesicles in the FAE of air-and CS-exposed mice and we analyzed the size and number of these vesicles by means of transmission electron microscopy.…”