CD300e-Mediated Immune Responses in Ulcerative Colitis

Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) characterized by chronic mucosal inflammation and ulceration predominantly affecting the rectum and colon, driven by a dysregulated immune response in which macrophages play a central role through cytokines production, leukocyte recruitment and epithelial damage. CD300e, an activating immunoreceptor expressed on myeloid cells, has been found implicated in shaping macrophage-mediated inflammatory responses. Previous work from our group demonstrated that in colorectal cancer (CRC), infiltrating macrophages display increased CD300e expression and a tumor-promoting profile. Conversely, CD300e deletion exerts a protective effect, as it re-establishes an anti-tumoral macrophages’ profile and, more broadly, a tumor microenvironment (TME) capable of hindering tumor growth. However, the role of this receptor in the earlier inflammatory stages that precede neoplastic transformation remains unclear. This thesis aims to investigate whether CD300e influences susceptibility to ulcerative colitis. We employed a murine model of dextran sodium sulfate (DSS)-induced colitis to compare clinical outcomes between CD300e-knockout (KO) and wild-type (WT) mice, and to evaluate the impact of CD300e on the inflammatory response. CD300e-deficient mice displayed reduced phenotypic manifestations, including milder weight loss, lower disease activity index (DAI) score, decreased splenomegaly, and longer colons. Flow cytometry analysis revealed differences in the immune infiltrate in the lamina propria, although these were relatively limited, between WT and KO mice. Overall, these findings suggest that CD300e is involved in the regulation of intestinal inflammation and that its absence mitigates disease severity in acute colitis.