Mast cell-expressed Mrgprb2/MRGPRX2 mediates gout pain and inflammation via a neuroimmune axis
1
Issued Date
2026-01-23
Resource Type
eISSN
23793708
Scopus ID
2-s2.0-105028345764
Pubmed ID
41574611
Journal Title
Jci Insight
Volume
11
Issue
2
Rights Holder(s)
SCOPUS
Bibliographic Citation
Jci Insight Vol.11 No.2 (2026)
Suggested Citation
Yang L., Liu C., Xiao J., Song Y., Chen H., Li D., Zou C., Hong T., Liu Y., Qi D., Limjunyawong N., Liu W., Qu L. Mast cell-expressed Mrgprb2/MRGPRX2 mediates gout pain and inflammation via a neuroimmune axis. Jci Insight Vol.11 No.2 (2026). doi:10.1172/jci.insight.201781 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/114513
Title
Mast cell-expressed Mrgprb2/MRGPRX2 mediates gout pain and inflammation via a neuroimmune axis
Corresponding Author(s)
Other Contributor(s)
Abstract
Acute severe joint pain is a major symptom in gouty arthritis (GA), and its adequate treatment represents an unmet medical need. Mrgprb2, a specific mast cell receptor, has been implicated in the generation of chronic pain by mobilizing mast cell degranulation, yet its significance in GA pain and joint inflammation is still not well defined. Here, we found that Mrgprb2 was expressed in mouse synovial mast cells. In a murine model of GA, acute blockade or genetic deletion of Mrgprb2 significantly attenuated arthritis pain and hyperexcitability of joint nociceptors with significant reductions in innate immune cell recruitment in the synovium. Under naive conditions, activation of synovial Mrgprb2 was sufficient to excite peripheral terminals of joint nociceptors to induce acute joint hypernociception via the mobilization of mast cell degranulation. Additionally, the level of the neuropeptide substance P (SP) was elevated in the synovium of GA model mice. Using humanized MRGPRX2-knockin mice, we revealed that SP contributed to joint pain and inflammation by activating mast cells through Mrgprb2/MRGPRX2. These findings suggest that synovial mast cell-expressed Mrgprb2/MRGPRX2 merits consideration as a key neuroimmune player and a potential therapeutic target for treating GA pain and joint inflammation.