Altered colonic intraepithelial lymphocyte composition and function in Crohn’s Disease

Abstract

Abstract Inflammatory bowel disease (IBD), which is subdivided into Ulcerative Colitis (UC) and Crohn’s Disease (CD), is a chronic inflammatory disease of the intestine with an incompletely understood pathogenesis. Studies to date have indicated that gender, microbiome, epithelial biology, and host immune responses contribute to disease. Intraepithelial lymphocytes (IELs) are T cells within the intestinal epithelium that are in close contact with bacterial populations; they are prime candidates to study the interaction between intestinal microbiota and host immunity. Thus, we evaluated IELs in pinch biopsies of uninflamed colon tissue from subjects with biopsy-proven IBD and controls that were undergoing routine colonoscopies. Using flow cytometry, we observed a significantly increased percentage of TCRγδ+ CD8αα and CD44+ IELs in CD compared to controls, suggesting an increase in activated IELs in individuals with CD. Mitogen-stimulated IELs from subjects with CD showed significantly increased TNF-α secretion. Furthermore, while none of our controls secreted IL-17, a subset of CD patients, all premenopausal women, had IELs that produced large amounts of this cytokine. Thus, our data indicate differences in IEL populations between CD, UC, and controls, which support the pathophysiologic differences between CD and UC. The different phenotypes suggest a role for these cells in the diagnosis of IBD. Additionally, given the inflammatory cytokine profile of IELs in subjects with CD, especially women, we propose that IL-17+ IELs are an interesting population of effector T cells that deserve further study to increase our understanding of this complex disease.