4.7 Article

USP19 suppresses inflammation and promotes M2-like macrophage polarization by manipulating NLRP3 function via autophagy

期刊

CELLULAR & MOLECULAR IMMUNOLOGY
卷 18, 期 10, 页码 2431-2442

出版社

CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-020-00567-7

关键词

Inflammasome; Autophagy; Macrophage polarization; Deubiquitinating enzyme; NLRP3

资金

  1. National Key Research and Development Project [2020YFA0908700]
  2. National Natural Science Foundation of China [31870862, 31700760]

向作者/读者索取更多资源

The study reveals that USP19 acts as an anti-inflammatory switch promoting M2-like macrophage polarization and inhibiting inflammatory responses by affecting NLRP3 activity through various mechanisms.
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-1 beta 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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据