Groslambert Marine, Py Bénédicte F
CIRI, Centre international de recherche en infectiologie, université de Lyon, 21, avenue Tony Garnier, 69007 Lyon, France - Inserm, U1111, Lyon, France - École normale supérieure de Lyon, 69000 Lyon, France - Université Lyon 1, Centre international de recherche en infectiologie, 69000 Lyon, France - CNRS, UMR5308, Lyon, France.
Med Sci (Paris). 2018 Jan;34(1):47-53. doi: 10.1051/medsci/20183401013. Epub 2018 Jan 31.
The innate immunity constitutes an efficient barrier by rapidly detecting pathogens and tissue damages through pattern recognition receptors including NLRP3. Moreover, inappropriate NLRP3 activation causes deleterious inflammation and contributes to various conditions including atherosclerosis, diabetes, gout and Alzheimer's diseases. NLRP3 assembles a multimeric inflammasome complex serving as an activation platform for caspase-1 that controls processing and release of cytosolic inflammatory factors and cytokines including IL-1β Inflammasome assembly is tightly controlled and requires coordinated NLRP3 priming, through cytokine or other pattern recognition receptors, followed by activation by cellular stress. Here, we describe recent advances in the understanding of the signalling pathways supporting the priming and activation of NLRP3, with a special focus on the key role of post-translational modifications of NLRP3, including phosphorylation and ubiquitination, in inflammasome regulation.
固有免疫通过模式识别受体（包括NLRP3）快速检测病原体和组织损伤，从而构成一道有效屏障。此外，NLRP3的不适当激活会导致有害炎症，并促成包括动脉粥样硬化、糖尿病、痛风和阿尔茨海默病在内的各种病症。NLRP3组装成多聚体炎性小体复合物，作为半胱天冬酶-1的激活平台，半胱天冬酶-1控制细胞溶质炎性因子和细胞因子（包括IL-1β）的加工和释放。炎性小体的组装受到严格控制，需要通过细胞因子或其他模式识别受体对NLRP3进行协同启动，随后由细胞应激激活。在此，我们描述了在理解支持NLRP3启动和激活的信号通路方面的最新进展，特别关注NLRP3的翻译后修饰（包括磷酸化和泛素化）在炎性小体调节中的关键作用。
