小柯机器人

美国圣裘德儿童研究医院Thirumala-Devi Kanneganti团队发现，NLRP12-泛凋亡体对血红素和PAMP的反应激活泛凋亡和病理。该研究于2023年6月1日在线发表于国际一流学术期刊《细胞》。

研究人员发现NLRP12在对血红素加PAMP或TNF的反应中驱动炎症体和泛凋亡体的激活、细胞死亡和炎症。TLR2/4通过IRF1介导的信号诱导Nlrp12表达，导致炎症体形成，诱导IL-1β和IL-18的成熟。炎症体也是更大的NLRP12-泛凋亡体的一个组成部分，通过caspase-8/RIPK3驱动炎症细胞死亡。删除Nlrp12可以保护小鼠免受急性肾脏损伤和溶血模型的死亡。总的来说，研究人员确定NLRP12是血红素加PAMP介导的泛凋亡、炎症和病理的重要细胞膜传感器，并表明NLRP12和该途径中的分子是溶血性和炎症性疾病的潜在药物靶点。

据介绍，细胞膜先天免疫传感器对宿主防御至关重要，并形成复合体，如炎症体和泛凋亡体，诱发炎症细胞死亡。传感器NLRP12与感染性和炎症性疾病有关，但它的激活诱因和在细胞死亡和炎症中的作用仍不清楚。

附：英文原文

Title: NLRP12-PANoptosome activates PANoptosis and pathology in response to heme and PAMPs

Author: Balamurugan Sundaram, Nagakannan Pandian, Raghvendra Mall, Yaqiu Wang, Roman Sarkar, Hee Jin Kim, R.K. Subbarao Malireddi, Rajendra Karki, Laura J. Janke, Peter Vogel, Thirumala-Devi Kanneganti

Issue&Volume: 2023-06-01

Abstract: Cytosolic innate immune sensors are critical for host defense and form complexes, such as inflammasomes and PANoptosomes, that induce inflammatory cell death. The sensor NLRP12 is associated with infectious and inflammatory diseases, but its activating triggers and roles in cell death and inflammation remain unclear. Here, we discovered that NLRP12 drives inflammasome and PANoptosome activation, cell death, and inflammation in response to heme plus PAMPs or TNF. TLR2/4-mediated signaling through IRF1 induced Nlrp12 expression, which led to inflammasome formation to induce maturation of IL-1β and IL-18. The inflammasome also served as an integral component of a larger NLRP12-PANoptosome that drove inflammatory cell death through caspase-8/RIPK3. Deletion of Nlrp12 protected mice from acute kidney injury and lethality in a hemolytic model. Overall, we identified NLRP12 as an essential cytosolic sensor for heme plus PAMPs-mediated PANoptosis, inflammation, and pathology, suggesting that NLRP12 and molecules in this pathway are potential drug targets for hemolytic and inflammatory diseases.

DOI: 10.1016/j.cell.2023.05.005

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00524-X