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

The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation.
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适配器 ASC 具有传播炎症的细胞外活性和“prionoid”活性。

DOI:
10.1038/ni.2913
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发表时间:
2014-08
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
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--
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微生物或危险信号触发炎性体传感器,其诱导适配器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,其诱导IL-1β细胞因子成熟和焦亡细胞死亡。在这里,我们发现,在焦亡后,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,ASC斑点的吞噬诱导溶酶体损伤、可溶性ASC的成核以及受体细胞中的半胱天冬酶-1和IL-1β活化。ASC斑点出现在来自发炎组织的体液中,并且针对ASC斑点的自身抗体在具有自身免疫性病理的患者和动物中发展。总之,这些发现揭示了ASC斑点的细胞外功能和细胞间通讯的新形式。
Microbes or danger signals trigger inflammasome sensors, which induce polymerization of the adapter ASC and assembly of an ASC speck. ASC specks recruit and activate caspase-1, which induces IL-1β cytokine maturation and pyroptotic cell death. Here we show that after pyroptosis ASC specks accumulate in the extracellular space, where they promote further IL-1β maturation. In addition, phagocytosis of ASC specks induces lysosomal damage, nucleation of soluble ASC as well as caspase-1 and IL-1β activation in the recipient cell. ASC specks appear in bodily fluids from inflamed tissues and autoantibodies against ASC specks develop in patients and animals with autoimmune pathologies. Together, these findings reveal extracellular functions of ASC specks and a novel form of cell-to-cell communication.
朊病毒样聚合是抗病毒免疫防御和炎症小体激活中信号转导的基础。
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