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Updated: Jun 30, 2025
Author Spotlight: Enhanced Method for Evaluating Analgesic Effects — Dual Hind Paw Carrageenan Injection in Mice
Published on: November 15, 2024
MS4A6D Promotes carrageenan-induced footpad swelling in mice through enhancing macrophages-derived inflammation
Jing Guo1, Chenhui Wang2, Qun Xiang3
1School of Medicine, Chongqing University, Chongqing 400033, China.
Abstract:
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 μL 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-1β in vivo. Moreover, macrophages from Ms4a6d-/- mice also showed a dramatical reduction of Il-1β 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-1β secretion in vivo. Collectively, MS4A6D aggravates CGN-induced footpad swelling in mice by enhancing NLRP3 inflammasome in macrophages and inducing the release of IL-1β, indicating that MS4A6D promotes the progression of acute inflammation.
Insights
Tetraspan MS4A6D aggravates carrageenan-induced swelling by enhancing NLRP3 inflammasome activation in macrophages. MS4A6D deficiency reduces IL-1β release and acute inflammation, highlighting its role in inflammatory responses.
Area of Science:
- Immunology
- Molecular Biology
Background:
- The tetraspan MS4A6D protein's role in macrophage-derived inflammation is not fully understood.
- Previous studies indicated MS4A6D interacts with MHC-II, promoting macrophage activation.
Purpose of the Study:
- To elucidate the precise function of MS4A6D in regulating macrophage-derived inflammation.
- To investigate the mechanism by which MS4A6D influences acute inflammatory responses.
Main Methods:
- Carrageenan-induced footpad swelling model in wild-type (WT) and Ms4a6d-deficient (Ms4a6d-/-) mice.
- Analysis of macrophage infiltration (F4/80+) and pro-IL-1β levels in inflamed tissues.
- In vitro assessment of IL-1β secretion from Ms4a6d-/- macrophages following NLRP3 inflammasome activation.
- Evaluation of MS4A6D mutants (C237G and Y241G) in the carrageenan model.
Main Results:
- Ms4a6d-/- mice exhibited significantly reduced footpad swelling compared to WT mice, similar to Nlrp3-/-, Casp-1-/-, and Ilr1-/- mice.
- Reduced macrophage infiltration and lower pro-IL-1β levels were observed in the footpads of Ms4a6d-/- mice.
- Macrophages from Ms4a6d-/- mice showed decreased IL-1β secretion upon NLRP3 inflammasome activation.
- MS4A6D mutants (C237G and Y241G) also significantly inhibited swelling and IL-1β secretion.
Conclusions:
- MS4A6D exacerbates carrageenan-induced footpad swelling by enhancing NLRP3 inflammasome activation in macrophages.
- MS4A6D promotes IL-1β release, thereby contributing to the progression of acute inflammation.
- Targeting MS4A6D may offer a therapeutic strategy for managing acute inflammatory conditions.
