MS4A6D Promotes carrageenan-induced footpad swelling in mice through enhancing macrophages-derived inflammation

作者全名：Guo, Jing; Wang, Chenhui; Xiang, Qun; Feng, Zeqing; Fei, Lei; Guo, Guoning; Shang, Yongjun; An, Yunfei; Ruan, Zhihua; Chen, Yongwen; Huang, Xiaoyong

作者地址：[Guo, Jing] Chongqing Univ, Sch Med, Chongqing 400033, Peoples R China; [Wang, Chenhui; Xiang, Qun; Feng, Zeqing; Fei, Lei; Chen, Yongwen; Huang, Xiaoyong] Third Mil Med Univ, Inst Immunol, PLA, Chongqing 400038, Peoples R China; [Wang, Chenhui] Beijing Inst Microbiol & Epidemiol, Beijing 100071, Peoples R China; [Xiang, Qun; Feng, Zeqing] Chongqing Int Inst Immunol, Chongqing 400026, Peoples R China; [Guo, Guoning; Shang, Yongjun] Kweichow Moutai Hosp, Dept Orthoped, Zunyi 564500, Guizhou, Peoples R China; [An, Yunfei] Chongqing Med Univ, Childrens Hosp, Dept Rheumatol & Immunol, Chongqing, Peoples R China; [Ruan, Zhihua] Third Mil Med Univ, Southwest Hosp, Dept Oncol, Chongqing 400038, Peoples R China; [Ruan, Zhihua] Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China

通信作者：Chen, YW; Huang, XY (通讯作者)，Third Mil Med Univ, Inst Immunol, PLA, Chongqing 400038, Peoples R China.; Ruan, ZH (通讯作者)，Third Mil Med Univ, Southwest Hosp, Dept Oncol, Chongqing 400038, Peoples R China.; Ruan, ZH (通讯作者)，Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing 400038, Peoples R China.

来源：MOLECULAR IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001225796700001

JCR分区：Q2

影响因子：3.2

年份：2024

卷号：169

期号：　

开始页：28

结束页：36

文献类型：Article

关键词：Carrageenan; NLRP3 inflammasome; IL-1 beta; Macrophages

摘要：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 100 mu L of 1% Carrageenan (CGN, w/v) plus CaCl2 (50 mM), 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-1 beta in vivo. Moreover, macrophages from Ms4a6d-/- mice also showed a dramatical reduction of Il-1 beta secretion following NLRP3 inflammsome activation in vitro. Interestingly, both Ms4a6dC237G mutant (Interruption of MS4A6D homodimerization) and Ms4a6dY241G mutant (deletion of heITAM motif) mice also significantly inhibited CGN-induced footpad swelling due to lower levels of Il-1 beta secretion in vivo. Collectively, MS4A6D aggravates CGN-induced footpad swelling in mice by enhancing NLRP3 inflammasome in macrophages and inducing the release of IL1 beta, indicating that MS4A6D promotes the progression of acute inflammation.

基金机构：National Natural Science Foundation of China (NSFC) [81971478, 82001693]; Chongqing Natural Science Fundation [CSTB2022NSCQ-MSX0219]

基金资助正文：This work was supported by The National Natural Science Foundation of China (NSFC, No. 81971478 and 82001693) and Chongqing Natural Science Fundation (CSTB2022NSCQ-MSX0219) .