Colitis aggravated by Mrgprb2 knockout is associated with altered immune response, intestinal barrier function and gut microbiota.

NEW FINDINGS: What is the central question of this study? What is the role of mas-related G protein-coupled receptor X2 (MRGPRX2/Mrgprb2) in ulcerative colitis in relation to the intestinal flora, intestinal barrier and immune response? What is the main finding and its importance? Knockout of mouse Mrgprb2 aggravates dextran sulfate sodium (DSS)-induced colitis, which is associated with altered gut microbiota and immune response and disruption of the intestinal barrier. MRGPRB2 may have a protective effect on DSS-induced colitis.

ABSTRACT: Ulcerative colitis (UC) is a chronic immune-related disease, and changes in the intestinal microbiota and damage to the intestinal barrier contribute to its pathogenesis. Mast cells (MCs) are widely distributed in the gastrointestinal tract and are thought to be related to the pathogenesis of UC. Human mas-related G protein-coupled receptor X2 (MRGPRX2) and its mouse homologue, Mrgprb2, are selectively expressed on MCs to recruit immune cells and modulate host defence against microbial infection. To investigate the role of Mrgprb2 in UC in mice, we compared the differences between Mrgprb2 knockout (b2KO) male mice and wild-type (WT) male mice with dextran sulfate sodium (DSS)-induced colitis in the severity of clinical symptoms, inflammatory cell infiltration, degree of intestinal barrier damage and composition of the intestinal flora. The results showed that weight loss, disease activity index score, colon shortening and colonic pathological damage were significantly increased in b2KO mice while MC activation, cytokine and chemokine secretion, and inflammatory cell infiltration were decreased. In addition, the abundance and diversity of the intestinal microbiota were reduced in b2KO mice. B2KO mice also exhibited a reduction of probiotics such as norank_f_Muribaculaceae and Lactobacillus and increase of harmful bacteria like Escherichia-Shigella. Intestinal mucosal barrier damage of b2KO mice was more severe than that of WT mice due to the attenuated expression of mucin-2 and occludin. These results demonstrated that MRGPRB2 may have a protective effect on DSS-induced colitis by altering the intestinal flora, participating in barrier repair and recruiting inflammatory cells to eliminate pathogens.