TRIM21促进炎性小体组装并导致自身炎症性疾病
TRIM21 facilitates inflammasome assembly and contributes to autoinflammatory disease.
摘要(中文译文)
炎症小体是胞质多蛋白复合物，促进炎性细胞因子白细胞介素（IL）-1β和IL-18的成熟与释放以及细胞焦亡。ASC（含CARD的凋亡相关斑点样蛋白）是炎症小体的核心衔接蛋白。ASC聚合对炎症小体组装至关重要，而ASC颗粒的释放可将炎症小体反应传播至旁邻细胞。然而，如何控制炎症小体和ASC颗粒的组装以限制慢性炎症及自身炎症性疾病的发生，目前仍不完全清楚。在此，我们发现E3泛素连接酶TRIM（三重基序蛋白）21——一种自身免疫性疾病中常见的自身抗原——参与炎症小体组装。具体而言，TRIM21结合并泛素化ASC，从而促进ASC/NLRP3相互作用、ASC聚合以及在人和小鼠巨噬细胞焦亡过程中含ASC/TRIM21颗粒的释放。此外，我们在人和小鼠自身炎症性疾病中检测到系统性ASC/TRIM21颗粒及自身抗体。因此，我们的研究结果揭示了TRIM21作为炎症小体组分和自身炎症驱动因素此前未被认识的作用。
Abstract
Inflammasomes are cytosolic multiprotein complexes facilitating the maturation and release of the inflammatory cytokines interleukin (IL)-1β and IL-18 and pyroptosis. ASC (apoptosis-associated-speck-like protein containing a CARD) is the central inflammasome adaptor. ASC polymerization is crucial for inflammasome assembly, and ASC particle release propagates inflammasome responses to bystander cells. However, control of inflammasome and ASC particle assembly to limit chronic inflammation and the emergence of autoinflammatory diseases is still incompletely understood. Here, we show that the E3 ubiquitin ligase TRIM (tripartite-motif-containing protein) 21, a common autoantigen in autoimmune diseases, is involved in inflammasome assembly. Specifically, TRIM21 binds to and ubiquitinates ASC to facilitate ASC/NLRP3 interactions, ASC polymerization and the release of ASC/TRIM21-containing particles during pyroptosis in human and mouse macrophages. Furthermore, we detect systemic ASC/TRIM21 particles and autoantibodies in human and mouse autoinflammatory disease. Thus, our findings highlight a previously unrecognized role of TRIM21 as an inflammasome component and driver of autoinflammation.
如何引用
AMA
Jessica Carriere, Chawon Yun, Sonal Khare, Sana Ismaeel, Elisabeth Jäger, Vinicius Dantas Martins, et al. TRIM21 facilitates inflammasome assembly and contributes to autoinflammatory disease.. Nature communications. 2026; doi:10.1038/s41467-026-73350-3.
APA
Jessica Carriere, Chawon Yun, Sonal Khare, Sana Ismaeel, Elisabeth Jäger, Vinicius Dantas Martins, et al (2026). TRIM21 facilitates inflammasome assembly and contributes to autoinflammatory disease.. Nature communications. https://doi.org/10.1038/s41467-026-73350-3
GB/T 7714
Jessica Carriere, Chawon Yun, Sonal Khare, Sana Ismaeel, Elisabeth Jäger, Vinicius Dantas Martins, et al. TRIM21 facilitates inflammasome assembly and contributes to autoinflammatory disease.[J]. Nature communications, 2026 doi:10.1038/s41467-026-73350-3.
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