The Role of the Immunoreceptor CD300e in Ulcerative Colitis and the Interplay with Gut Microbiota

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven by dysregulated interactions between immune cells, epithelial barrier, and gut microbiota. Intestinal macrophages are critically involved in sensing intestinal microbiota perturbations, and their activation state influences intestinal inflammation. Recently, we identified the myeloid-specific immunoreceptor CD300e as a possible regulator of myeloid response in UC. Using a CD300e knockout (KO) mouse line, and a dextran sodium sulfate (DSS)-induced acute colitis model, this thesis aimed at investigating how the receptor contributes to colitis pathogenesis. Results indicate that CD300e deficiency confers significant protection against colitis, as highlighted by reduced weight loss, lower disease activity, and preserved colonic tissue integrity in KO mice compared to wild-type (WT) counterparts. Additionally, immunophenotyping evaluation by flow cytometry revealed decreased infiltration of neutrophils, paired with increased infiltration of macrophages in the colon lamina propria of CD300e-deficient mice. Further analyses also highlighted a reduced expression of pro-inflammatory mediators as CXCL1, TNF-α, and IL-1β, in the absence of CD300e, indicating attenuated intestinal inflammation. Previous work from the lab has demonstrated that CD300e KO mice harbor a distinct gut microbiota composition, enriched in probiotic bacteria. Accordingly, fecal microbiota transplantation from CD300e KO donors into WT recipients significantly ameliorates colitis, suggesting the involvement of CD300e in shaping gut microbial ecology towards a protective community. These findings identify CD300e as a critical mediator of host immunity-microbiota axis and regulator of intestinal inflammation.