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衔接子 ASC 具有传播炎症的细胞外和“朊病毒样”活性。

The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation.

机构信息

Institute of Innate Immunity, University Hospitals, University of Bonn, Bonn, Germany.

1] Department of Immunology and Rheumatology, Hannover Medical School, Hannover, Germany. [2] Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

出版信息

Nat Immunol. 2014 Aug;15(8):727-37. doi: 10.1038/ni.2913. Epub 2014 Jun 22.

Abstract

Microbes or danger signals trigger inflammasome sensors, which induce polymerization of the adaptor ASC and the assembly of ASC specks. ASC specks recruit and activate caspase-1, which induces maturation of the cytokine interleukin 1β (IL-1β) and pyroptotic cell death. Here we found that after pyroptosis, ASC specks accumulated in the extracellular space, where they promoted further maturation of IL-1β. In addition, phagocytosis of ASC specks by macrophages induced lysosomal damage and nucleation of soluble ASC, as well as activation of IL-1β in recipient cells. ASC specks appeared in bodily fluids from inflamed tissues, and autoantibodies to ASC specks developed in patients and mice with autoimmune pathologies. Together these findings reveal extracellular functions of ASC specks and a previously unknown form of cell-to-cell communication.

摘要

微生物或危险信号触发炎性体传感器,诱导衔接子 ASC 的聚合和 ASC 斑点的组装。ASC 斑点募集并激活半胱天冬酶-1,诱导细胞因子白细胞介素 1β(IL-1β)和细胞焦亡的成熟。在这里,我们发现细胞焦亡后,ASC 斑点在细胞外空间积累,在那里它们促进 IL-1β的进一步成熟。此外,巨噬细胞对 ASC 斑点的吞噬作用诱导溶酶体损伤和可溶性 ASC 的成核,以及受体细胞中 IL-1β的激活。ASC 斑点出现在炎症组织的体液中,自身抗体也在自身免疫性疾病患者和小鼠中发展。这些发现共同揭示了 ASC 斑点的细胞外功能和一种以前未知的细胞间通讯形式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b655/4116676/ebf7b757f2d4/nihms-592129-f0001.jpg

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