PDF(Pubmed)
Abstract：
NLRs constitute a large, highly conserved family of cytosolic pattern recognition receptors that are central to health and disease, making them key therapeutic targets. NLRC5 is an enigmatic NLR with mutations associated with inflammatory and infectious diseases, but little is known about its function as an innate immune sensor and cell death regulator. Therefore, we screened for NLRC5\'s role in response to infections, PAMPs, DAMPs, and cytokines. We identified that NLRC5 acts as an innate immune sensor to drive inflammatory cell death, PANoptosis, in response to specific ligands, including PAMP/heme and heme/cytokine combinations. NLRC5 interacted with NLRP12 and PANoptosome components to form a cell death complex, suggesting an NLR network forms similar to those in plants. Mechanistically, TLR signaling and NAD+ levels regulated NLRC5 expression and ROS production to control cell death. Furthermore, NLRC5-deficient mice were protected in hemolytic and inflammatory models, suggesting that NLRC5 could be a potential therapeutic target.
摘要：
NLR构成了一个很大的，对健康和疾病至关重要的高度保守的胞浆模式识别受体家族，使它们成为关键的治疗靶点。NLRC5是一种神秘的NLR，具有与炎症和传染病相关的突变，但对其作为先天免疫传感器和细胞死亡调节因子的功能知之甚少。因此,我们筛查了NLRC5在感染反应中的作用，PAMPs,DAMPs,和细胞因子。我们发现NLRC5作为驱动炎性细胞死亡的先天免疫传感器，全角下垂,响应特定的配体，包括PAMP/血红素和血红素/细胞因子组合。NLRC5与NLRP12和PANphosome组件相互作用形成细胞死亡复合物，这表明NLR网络的形式与植物中的类似。机械上,TLR信号和NAD+水平调节NLRC5表达和ROS产生以控制细胞死亡。此外，NLRC5缺陷小鼠在溶血和炎症模型中受到保护，表明NLRC5可能是一个潜在的治疗靶点。
