NLRP3 licenses NLRP11 for inflammasome activation in human macrophages.
NLRP3 licenses NLRP11 for inflammasome activation in human macrophages.
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DOI：
10.1038/s41590-022-01220-3
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发表时间：
2022-06
影响因子：
30.5
通讯作者：
Stehlik, Christian
中科院分区：
文献类型：
--
作者：
Gangopadhyay, Anu;Devi, Savita;Tenguria, Shivendra;Carriere, Jessica;Huyen Nguyen;Jager, Elisabeth;Khatri, Hemisha;Chu, Lan H.;Ratsimandresy, Rojo A.;Dorfleutner, Andrea;Stehlik, Christian
应激和危险信号的细胞内感知通过触发炎性小体组装、半胱天冬酶-1激活和细胞死亡以及白细胞介素1β（IL-1β）、IL-18和危险信号的释放来启动炎性先天免疫应答。NLRP 3广泛感知感染模式和无菌危险信号，导致NLRP 3炎性体的紧密协调和调节组装，但确切机制尚不完全清楚。在这里，我们将NLRP 11鉴定为人类巨噬细胞中NLRP 3炎性体的重要组成部分。NLRP 11与NLRP 3和ASC相互作用，并且NLRP 11的缺失通过阻止炎性体组装、NLRP 3和ASC聚合、半胱天冬酶-1活化、焦亡和细胞因子释放而特异性地阻止NLRP 3炎性体活化，但不影响其他炎性体。恢复NLRP 11的表达，但不是缺乏PYRIN结构域（PYD）的NLRP 11，恢复炎性小体活化。NLRP 11也是由NLRP 3突变驱动的炎性体反应所必需的，NLRP 3突变导致cryopyrin相关周期性综合征（CAPS）。由于NLRP 11在小鼠中不表达，我们的观察结果强调了人类炎性小体调控的特殊复杂性。Stehlik及其同事表明，NLRP 11是人类巨噬细胞中NLRP 3炎性体的重要组成部分。
Intracellular sensing of stress and danger signals initiates inflammatory innate immune responses by triggering inflammasome assembly, caspase-1 activation and pyroptotic cell death as well as the release of interleukin 1β (IL-1β), IL-18 and danger signals. NLRP3 broadly senses infectious patterns and sterile danger signals, resulting in the tightly coordinated and regulated assembly of the NLRP3 inflammasome, but the precise mechanisms are incompletely understood. Here, we identified NLRP11 as an essential component of the NLRP3 inflammasome in human macrophages. NLRP11 interacted with NLRP3 and ASC, and deletion of NLRP11 specifically prevented NLRP3 inflammasome activation by preventing inflammasome assembly, NLRP3 and ASC polymerization, caspase-1 activation, pyroptosis and cytokine release but did not affect other inflammasomes. Restored expression of NLRP11, but not NLRP11 lacking the PYRIN domain (PYD), restored inflammasome activation. NLRP11 was also necessary for inflammasome responses driven by NLRP3 mutations that cause cryopyrin-associated periodic syndrome (CAPS). Because NLRP11 is not expressed in mice, our observations emphasize the specific complexity of inflammasome regulation in humans. Stehlik and colleagues show that NLRP11 is an essential component of the NLRP3 inflammasome in human macrophages.
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影响因子：
64.5
作者：
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DOI：
10.4049/jimmunol.0802367
发表时间：
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期刊：
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影响因子：
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Stehlik C
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发表时间：
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期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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DOI：
10.1073/pnas.0611496104
发表时间：
2007-05-08
影响因子：
11.1
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通讯作者：
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