Mrgprb2, the mouse ortholog of human MRGPRX2, is a mast-cell-specific G-protein-coupled receptor. It plays a crucial role in non-IgE-mediated mast cell activation, participating in various physiological and pathological processes such as neuro-immune regulation, inflammation, and pain response. Signaling through Mrgprb2 activates multiple pathways, and its activation can lead to the release of pro-inflammatory cytokines, chemokines, and enzymes like tryptase, which are involved in the development of inflammation [1,2,3,4,5,6,7,8,9,10].

In atopic dermatitis (AD) mouse models, Mrgprb2-conditional knockout (Mrgprb2-/-) mice showed milder phenotypes and less inflammatory infiltration compared to wild-type mice. Tryptase released by MRGPRX2/MRGPRB2 activation contributed to type 2 cytokine release and AD-related inflammation [1]. In Modic changes models, Mrgprb2 knockout inhibited mast cell activation, reducing the degree of Modic changes, and Mrgprb2-activated mast cells regulated immune niches by influencing macrophage polarization [3]. In acute colitis models, Mrgprb2-/-mice had impaired DSS-induced neutrophil influx and less severe colitis progression, indicating its role in colitis pathophysiology [5]. Alcohol-withdrawal-induced headache behaviors were absent in Mrgprb2-deficient mice, suggesting its role in this condition [7]. Mrgprb2-deficiency also decreased itch in allergic contact dermatitis models [8].

In conclusion, Mrgprb2 is a key mediator in mast-cell-related immune and inflammatory responses. Gene knockout mouse models have significantly advanced our understanding of its role in diseases such as atopic dermatitis, Modic changes, acute colitis, alcohol-withdrawal-associated headache, and allergic contact dermatitis. These studies provide potential therapeutic targets for treating these conditions by modulating Mrgprb2-mediated pathways.