| First Author | Guo J | Year | 2024 |
| Journal | Mol Immunol | Volume | 169 |
| Pages | 28-36 | PubMed ID | 38493579 |
| Mgi Jnum | J:346402 | Mgi Id | MGI:7616155 |
| Doi | 10.1016/j.molimm.2024.03.001 | Citation | Guo J, et al. (2024) MS4A6D Promotes carrageenan-induced footpad swelling in mice through enhancing macrophages-derived inflammation. Mol Immunol 169:28-36 |
| abstractText | Our previous work has demonstrated that the tetraspan MS4A6D interacts with MHC-II to be a complex that promotes macrophage activation (Mol Immunol. 2023; 160: 121-132), however, the exact role of MS4A6D in controlling macrophage-derived inflammation is still poorly understood. Here, we showed that Ms4a6d-deficient (Ms4a6d(-/-)) mice manifested a lower level of footpad swelling induced by subcutaneous injection of 100muL of 1% Carrageenan (CGN, w/v) plus CaCl(2) (50mM), a phenomenon that is similar to Nlrp3(-/-), Casp-1(-/-), and Ilr1(-/-) mice. Mechanistically, F4/80(+) macrophages infiltrated in the footpad tissues of the Ms4A6d(-/-) mice was significantly lower than that of the WT littermates, leading to dramatically lower levels of proIL-1beta in vivo. Moreover, macrophages from Ms4a6d(-/-) mice also showed a dramatical reduction of Il-1beta secretion following NLRP3 inflammsome activation in vitro. Interestingly, both Ms4a6d(C237G) mutant (Interruption of MS4A6D homodimerization) and Ms4a6d(Y241G) mutant (deletion of heITAM motif) mice also significantly inhibited CGN-induced footpad swelling due to lower levels of Il-1beta secretion in vivo. Collectively, MS4A6D aggravates CGN-induced footpad swelling in mice by enhancing NLRP3 inflammasome in macrophages and inducing the release of IL-1beta, indicating that MS4A6D promotes the progression of acute inflammation. |
