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CD11B deficiency promotes inflammasome activation in macrophages and aggravates MSU-induced joint inflammation in mice


Driss Ehirchiou, Ilaria Bernabei, Veronique Chobaz, Sonia Nasi, Mariela Castelblanco , Alexander So , Hans Acha-Orbea, Thomas Hugle, Li Zhang, Nathalie Busso



Laboratory Of Rheumatology, CHUV Lausanne



In gout, monosodium urate (MSU) crystals are taken up by macrophages, triggering the activation of the NLRP3 inflammasome and the production of IL-1 β. In this study, we report a specific role of integrin CD11b in inflammasome activation in macrophages stimulated by MSU. We demonstrate that CD11b-deficient mice developed exacerbated gouty arthritis with increased recruitment of leukocytes in the joint and higher IL-1 β levels in the sera. In macrophages, genetic deletion of CD11b induced a shift of macrophage metabolism from oxidative phosphorylation to glycolysis, thus decreasing the generation of ATP and increasing the production of IL-6 and IL-1 β and upon MSU stimulation in vitro. Treating macrophages with a CD11b agonist, LA1, inhibited the release of IL-1 β in vitro and in vivo and attenuated the severity of experimental gouty arthritis. Taken together, our data identified the CD11b integrin as a principal cell membrane receptor that mediates inflammasome activation by MSU crystal in macrophages, which could be a potential therapeutic target to treat gouty arthritis in human patients.