(P150) IMMUNE MODULATION BY MACROPHAGE GALACTOSE C-TYPE LECTIN ALLEVIATE MURINE MODEL OF COLITIS

CD301, also known as MGL (macrophage galactose C-type lectin), is a type II transmembrane glycoprotein in the C-type lectin receptor family that recognizes terminal N-acetyl galactosamine (GalNAc) residues predominantly on serine or threonine of mucins. While a single human gene encodes CD301, mice have two corresponding homologs, CD301a and CD301b, with differing glycan binding specificity. CD301b specifically binds terminal O-GalNAc. CD301b-expressing cells play important roles in immune regulation within tumor microenvironments and the submucosa of GI and respiratory tracts. Activation of CD301b dampens immune responses by up-regulating the production of IL-10, promoting Treg differentiation, and suppressing T cell activation. Imbalances in the gut microbiota can contribute to inflammatory bowel diseases (IBD) pathogeneses, suggesting an interplay between the gut microbiota and the host immune system, influencing the onset and prognosis of IBD. Microbes can mimic host cellular surface moieties to regulate host immune cells, aiding their immune evasion. Based on the prior research and our preliminary data, we hypothesized that CD301b-Tn interaction is an essential immunoregulatory mechanism to maintain gut-microbiome homeostasis. Thus, our objective is to identify the role of Tn-CD301b signaling and CD301b+ immune cells in colitis pathogenesis and dysbiosis in the gut. We demonstrate that the CD301b+ immune cells regulate the gut immune environment and microbiota. When colitis is induced in mouse models via DSS, CD301b+ cells are recruited to the colon lamina propria and dampen immune responses. CD301b-depleted mice have shown a significantly worse prognosis of DSS-induced colitis compared to their wild-type litter mates, as these mice did not recover from DSS concentrations of as little as 3%. Our data indicate that CD301(b) modulation in the GI tract has strong therapeutic implications for IBD treatments.