The Role of Ly49E Expression on Intestinal Intraepithelial Lymphocytes in the Development and Progression of Inflammatory Bowel Diseases, Tumor Immune Response and Bacterial Infection

The Ly49E NK receptor is a unique inhibitory receptor, presenting with a high degree of conservation among mouse strains and expression on both NK and intraepithelial-localized T cells. Amongst intraepithelial-localized T cells, we show that the Ly49E receptor is abundantly expressed on CD8αα-expressing innate-like intestinal intraepithelial lymphocytes (iIELs), with even higher expression in the colon as compared to the small intestine. CD8αα-positive iIELs contribute to front-line defense at the mucosal barrier. Here, we have investigated a potential role for Ly49E expression on iIELs in the context of inflammatory bowel diseases, tumor immune response, and bacterial infection. Making use of Ly49E-deficient mice, we show that Ly49E expression on iIELs does not influence the development or progression of DSS- or TNBS-induced colitis, nor that of TNF^ΔARE ileitis. Exploring a role for Ly49E in intestinal tumor immune response, we made use of the azoxymethane-induced colorectal cancer model and Apc^Min/+  transgenic mice. We show that colorectal cancer development is unaltered between Ly49E WT and Ly49E KO mice, and that Apc^Min/+ Ly49E KO mice display with a similar tumor immune response as compared with Apc^Min/+ Ly49E WT mice. Finally, investigating a role for Ly49E expression on iIELs in bacterial infection, we show that Ly49E expression does not affect the kinetics of Citrobacter rodentium or Salmonella typhimurium infection. In conclusion, although Ly49E is highly expressed on CD8αα^pos iIELs of the colon and small intestine, this NK receptor does not influence the development or progression of inflammatory bowel diseases, intestinal tumor immune response or intestinal bacterial infection.