Mucosal T Cells Bearing TCRγδ Play a Protective Role in Intestinal Inflammation

Abstract

Intestinal intraepithelial lymphocytes (IEL) bearing TCRγδ represent a major T cell population in the murine intestine. However, the role of γδ IEL in inflammatory bowel diseases (IBD) remains controversial. In this study, we show that γδ IEL is an important protective T cell population against IBD. γδ T cell-deficient (Cδ−/−) mice developed spontaneous colitis with age and showed high susceptibility to Th1-type 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis at a young age. Transfer of γδ IEL to Cδ−/− mice ameliorated TNBS-induced colitis, which correlated with decrease of IFN-γ and TNF-α production and an increase of TGF-β production by IEL. Furthermore, a high level of IL-15, which inhibits activation-induced cell death to terminate inflammation, was expressed more in intestinal epithelial cells (EC) from TNBS-treated Cδ−/− mice than in those from wild-type mice. EC from wild-type mice significantly suppressed the IFN-γ production of IEL from TNBS-treated Cδ−/− mice, whereas EC from TNBS-treated Cδ−/− mice did not. These data indicate that γδ IEL play important roles in controlling IBD by regulating mucosal T cell activation cooperated with EC function. Our study suggests that enhancement of regulatory γδ T cell activity is a possible new cell therapy for colitis.

Streptococcus thermophilus NCIMB 41856 ameliorates signs of colitis in an animal model of inflammatory bowel disease

“…Furthermore, they regulate proliferation and differentiation of epithelial cells and play a role in induction of apoptosis in senescent or infected cells, allowing for rapid regeneration and reducing the risk of leaks (Guy-Grand et al, 1998). IELs are a mixed population of cells with different phenotypes having different roles in intestinal inflammation, some of which have been shown to be protective against colitis in animal models of disease (Chen et al, 2002;Inagaki-Ohara et al, 2004;Roselli et al, 2009). Further phenotypical and functional analyses are required in order to accurately determine the role that this increased population of CD8 + IELs play in inflammation.…”

Interleukin‐17A is required to suppress invasion of Salmonella enterica serovar Typhimurium to enteric mucosa

“…22,23 Dissected small segments of the intestines were incubated at 37°for 30 min in an RPMI-1640 medium (Sigma-Aldrich, St Louis, MO) containing 10% fetal calf serum and 1 mM dithiothreitol with vigorous shaking. The tissue suspension was passed through a nylon mesh to remove debris and centrifuged through a 25/40/75% discontinuous Percoll (Sigma-Aldrich) gradient at 600 g at 20°for 20 min.…”

Dynamic migration of γδ intraepithelial lymphocytes requires occludin

“…Although the majority of these IELs express the γδ T cell receptor, and epidermal γδ IELs have been studied extensively (1)(2)(3)(4), the functions of intestinal γδ IELs remain poorly understood. Some studies have shown that γδ IELs contribute to progression of immune-mediated colitis (5)(6)(7); other data suggest that γδ IELs contribute to mucosal homeostasis (8,9) by secreting keratinocyte growth factor (10,11) and antimicrobial peptides (12,13), suppressing CD4 + T-cell expansion through TGF-β and IL-10 production (8,9) and promoting barrier maintenance via poorly understood mechanisms (13)(14)(15). These observations and the small number of IELs relative to intestinal epithelial cells are difficult to reconcile with the widely held belief that γδ IELs have limited motility (1,16).…”