11月3日免疫学专业期刊《免疫学杂志》（Journal of Immunology）在线发表了中科院上海生科院生化与细胞所孙兵研究组最新研究论文。

天然免疫反应作为机体防御病原体的第一道防线，主要通过模式识别受体PRR来识别病原体编码的病原相关分子模式PAMP，其中Nod样受体（NLR）是模式识别受体中非常重要的一类。这些受体可以识别不同病原体的分子模式，通过信号转导诱导许多免疫和炎症基因的表达，从而使机体建立抵御外界病原体的先天免疫状态。NLRP3作为NLR的一员，在激活之后能够通过与其接头蛋白ASC相互作用，招募Pro-caspase-1，形成蛋白复合物“炎症小体”，进而对Pro-IL-1β等底物进行切割使其成熟并释放到胞外发挥功能。虽然研究发现许多病原体或体内危险信号都能激活NLRP3炎症小体，但是对于NLRP3炎症小体的调控过程还不清楚。

孙兵研究组在以前的研究中发现TRIM30能够通过降解TLR信号通路中的重要分子TAB2/TAB3来负性调控TLR信号通路。在本研究中，胡宇和毛开睿博士发现TRIM30也能够负性调节NLRP3炎症小体的激活。在用各种刺激剂激活NLRP3炎症小体的情况下，抑制TRIM30的表达能够促进caspase-1的活化进而增强IL-1β的成熟和分泌。同时他们还发现TRIM30可能是通过影响ROS的产生来调控NLRP3炎症小体的激活。在体内，运用MSU晶体诱导的小鼠腹腔炎模型也发现，在TRIM30转基因小鼠体内IL-1β的分泌和嗜中性粒细胞的浸润都明显下降。通过体内外实验他们证明了TRIM30能够负性调控NLRP3炎症小体。

此项研究成果得到科技部、国家自然科学基金的资金资助。

英文摘要：

The Journal of Immunology, 2010, doi:10.4049/jimmunol.1001099

Tripartite-Motif Protein 30 Negatively Regulates NLR Family, Pyrin Domain-Containing 3 Inflammasome Activation by Modulating Reactive Oxygen Species Production
Yu Hu,*,1 Kairui Mao,*,1 Yan Zeng, Shuzhen Chen,* Zhiyun Tao,* Chen Yang,* Shuhui Sun, Xiaodong Wu,* Guangxun Meng, and Bing Sun*,

*Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences; and Fudan University School of Medicine, Shanghai, China

The NLR family, pyrin domain-containing 3 (NLRP3) inflammasome is critical for caspase-1 activation and the proteolytic processing of pro–IL-1β. However, the mechanism that regulates NLRP3 inflammasome activation remains unclear. In this paper, we demonstrate that tripartite-motif protein 30 (TRIM30) negatively regulates NLRP3 inflammasome activation. After stimulation with ATP, an agonist of the NLRP3 inflammasome, knockdown of TRIM30 enhanced caspase-1 activation and increased production of IL-1β in both J774 cells and bone marrow-derived macrophages. Similarly with ATP, knockdown of TRIM30 increased caspase-1 activation and IL-1β production triggered by other NLRP3 inflammasome agonists, including nigericin, monosodium urate, and silica. Production of reactive oxygen species was increased in TRIM30 knockdown cells, and its increase was required for enhanced NLRP3 inflammasome activation, because antioxidant treatment blocked excess IL-1β production. Conversely, overexpression of TRIM30 attenuated reactive oxygen species production and NLRP3 inflammasome activation. Finally, in a crystal-induced NLRP3 inflammasome-dependent peritonitis model, monosodium urate-induced neutrophil flux and IL-1β production was reduced significantly in TRIM30 transgenic mice as compared with that in their nontransgenic littermates. Taken together, our results indicate that TRIM30 is a negative regulator of NLRP3 inflammasome activation and provide insights into the role of TRIM30 in maintaining inflammatory responses.