TY - JOUR TI - USP19 suppresses inflammation and promotes M2-like macrophage polarization by manipulating NLRP3 function via autophagy AU - Liu, Tao AU - Wang, Liqiu AU - Liang, Puping AU - Wang, Xiaojuan AU - Liu, Yukun AU - Cai, Jing AU - She, Yuanchu AU - Wang, Dan AU - Wang, Zhi AU - Guo, Zhiyong AU - Bates, Samuel AU - Xia, Xiaojun AU - Huang, Junjiu AU - Cui, Jun T2 - Cellular & Molecular Immunology AB - Macrophage polarization to proinflammatory M1-like or anti-inflammatory M2-like cells is critical to mount a host defense or repair tissue. The exact molecular mechanisms controlling this process are still elusive. Here, we report that ubiquitin-specific protease 19 (USP19) acts as an anti-inflammatory switch that inhibits inflammatory responses and promotes M2-like macrophage polarization. USP19 inhibited NLRP3 inflammasome activation by increasing autophagy flux and decreasing the generation of mitochondrial reactive oxygen species. In addition, USP19 inhibited the proteasomal degradation of inflammasome-independent NLRP3 by cleaving its polyubiquitin chains. USP19-stabilized NLRP3 promoted M2-like macrophage polarization by direct association with interferon regulatory factor 4, thereby preventing its p62-mediated selective autophagic degradation. Consistent with these observations, compared to wild-type mice, Usp19−/− mice had decreased M2-like macrophage polarization and increased interleukin-1β secretion, in response to alum and chitin injections. Thus, we have uncovered an unexpected mechanism by which USP19 switches the proinflammatory function of NLRP3 into an anti-inflammatory function, and suggest that USP19 is a potential therapeutic target for inflammatory interventions. DA - 2020/10/23/ PY - 2020 DO - 10.1038/s41423-020-00567-7 DP - www.nature.com SP - 1 EP - 12 LA - en SN - 2042-0226 UR - https://www.nature.com/articles/s41423-020-00567-7 Y2 - 2020/10/23/21:17:13 ER -