| First Author | Roy S | Year | 2022 |
| Journal | J Invest Dermatol | PubMed ID | 35644498 |
| Mgi Jnum | J:326597 | Mgi Id | MGI:7314025 |
| Doi | 10.1016/j.jid.2022.05.005 | Citation | Roy S, et al. (2022) Role of MrgprB2 in Rosacea-Like Inflammation in Mice: Modulation by beta-Arrestin 2. J Invest Dermatol |
| abstractText | Cathelicidin LL-37mediated activation of mast cells (MCs) has been implicated in the pathogenesis of rosacea, but the receptor involved and the mechanism of its activation and regulation remain unknown. We found that skin biopsies from patients with rosacea display higher frequencies of MCs expressing MRGPRX2 (mouse counterpart MrgprB2) than normal skin. Intradermal injection of LL-37 in wild-type mice resulted in MC recruitment, expression of inflammatory mediators, and development of rosacea-like inflammation. These responses were substantially reduced in MrgprB2(/) mice and abolished in MC deficient W(sh)/W(sh) mice. beta-arrestin 2 is an adaptor protein that regulates G protein-coupled receptor function by receptor desensitization and also by activation of downstream signaling. We found that LL-37induced rosacea-like inflammation was significantly reduced in mice with MC-specific deletion of beta-arrestin 2 compared with that in control mice. Interestingly, the absence of beta-arrestin 2 resulted in enhanced cofilin phosphorylation and substantial inhibition of LL-37induced chemotaxis of mouse peritoneal MCs. Furthermore, LL-37induced extracellular signalregulated kinase 1/2 phosphorylation, NF-kappaB activation, and proinflammatory cytokine/chemokine production were reduced in beta-arrestin 2(/) peritoneal MCs compared with those in wild-type cells. These findings suggest that MRGPRX2/B2 participates in rosacea and that beta-arrestin 2 contributes to its pathogenesis by promoting cofilin dephosphorylation, extracellular signalregulated kinase 1/2 and NF-kappaB phosphorylation, MC chemotaxis, and chemokine/cytokine generation. |
