Mrgprb2, a Mas-related G-protein-coupled receptor, is expressed on mast cells. It serves as a crucial mediator in various non-IgE-dependent mast cell activation pathways. Activation of Mrgprb2 can lead to mast cell degranulation, releasing substances like histamine, tryptase, and cytokines, which are involved in immune-related processes such as neuroimmune regulation, inflammation, and pain [2,5,7].

Mrgprb2-conditional knockout (Mrgprb2-/-) mice have been used in multiple studies to reveal its role. In an MC903-induced AD mouse model, Mrgprb2-/-mice showed milder phenotypes and less inflammatory infiltration, indicating that MRGPRB2-tryptase axis is involved in type 2 inflammation development in AD [1]. In Modic change models, Mrgprb2 knockout inhibited mast cell activation and reduced the degree of Modic changes, as Mrgprb2-activated mast cells regulate immune niches by influencing macrophage polarization [3]. In acute colitis models, loss of Mrgprb2-mediated signaling impaired DSS-induced neutrophil influx and impacted acute colitis progression [4]. In alcohol-withdrawal-associated headache models, Mrgprb2-deficient mice did not show headache-related behaviors during alcohol withdrawal, suggesting that Mrgprb2 in dura mater mast cells is involved in this process [6]. Baicalin-induced pseudo-allergy was absent in Mrgprb2-knockout mice, indicating baicalin induces pseudo-allergy via Mrgprb2 in mice [8].

In conclusion, Mrgprb2 plays a vital role in mast-cell-mediated immune responses, inflammation, and pain-related processes. Studies using Mrgprb2 KO/CKO mouse models have provided insights into its functions in diseases such as atopic dermatitis, Modic changes, acute colitis, alcohol-withdrawal-associated headache, and pseudo-allergic reactions, suggesting it could be a potential therapeutic target for these conditions.

References:

1. Jia, Tao, Che, Delu, Zheng, Yi, An, Jingang, Geng, Songmei. 2023. Mast Cells Initiate Type 2 Inflammation through Tryptase Released by MRGPRX2/MRGPRB2 Activation in Atopic Dermatitis. In The Journal of investigative dermatology, 144, 53-62.e2. doi:10.1016/j.jid.2023.06.201. https://pubmed.ncbi.nlm.nih.gov/37482287/

2. Bawazir, Maram, Amponnawarat, Aetas, Hui, Yvonne, Oskeritzian, Carole A, Ali, Hydar. 2022. Inhibition of MRGPRX2 but not FcεRI or MrgprB2-mediated mast cell degranulation by a small molecule inverse receptor agonist. In Frontiers in immunology, 13, 1033794. doi:10.3389/fimmu.2022.1033794. https://pubmed.ncbi.nlm.nih.gov/36275683/

3. Ji, Zhongyin, Li, Jie, Tao, Siyue, Liu, Junhui, Zhao, Fengdong. 2024. Mrgprb2-mediated mast cell activation exacerbates Modic changes by regulating immune niches. In Experimental & molecular medicine, 56, 1178-1192. doi:10.1038/s12276-024-01230-1. https://pubmed.ncbi.nlm.nih.gov/38689089/

4. Van Remoortel, Samuel, Lambeets, Lana, De Winter, Benedicte, Martinez, Sales Ibiza, Timmermans, Jean-Pierre. 2024. Mrgprb2-dependent Mast Cell Activation Plays a Crucial Role in Acute Colitis. In Cellular and molecular gastroenterology and hepatology, 18, 101391. doi:10.1016/j.jcmgh.2024.101391. https://pubmed.ncbi.nlm.nih.gov/39179175/

5. Green, Dustin P, Limjunyawong, Nathachit, Gour, Naina, Pundir, Priyanka, Dong, Xinzhong. 2019. A Mast-Cell-Specific Receptor Mediates Neurogenic Inflammation and Pain. In Neuron, 101, 412-420.e3. doi:10.1016/j.neuron.2019.01.012. https://pubmed.ncbi.nlm.nih.gov/30686732/

6. Son, Hyeonwi, Zhang, Yan, Shannonhouse, John, Gomez, Ruben, Kim, Yu Shin. 2023. Mast-cell-specific receptor mediates alcohol-withdrawal-associated headache in male mice. In Neuron, 112, 113-123.e4. doi:10.1016/j.neuron.2023.09.039. https://pubmed.ncbi.nlm.nih.gov/37909038/

7. McNeil, Benjamin D, Pundir, Priyanka, Meeker, Sonya, Kulka, Marianna, Dong, Xinzhong. 2014. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. In Nature, 519, 237-41. doi:10.1038/nature14022. https://pubmed.ncbi.nlm.nih.gov/25517090/

8. Wang, Jue, Zhang, Yongjing, Che, Delu, Qin, Qiaohong, Wang, Nan. 2020. Baicalin induces Mrgprb2-dependent pseudo-allergy in mice. In Immunology letters, 226, 55-61. doi:10.1016/j.imlet.2020.07.006. https://pubmed.ncbi.nlm.nih.gov/32707128/