Cutting Edge: miR-223 and EBV miR-BART15 Regulate the NLRP3 Inflammasome and IL-1β Production
Cutting Edge: miR-223 and EBV miR-BART15 Regulate the NLRP3 Inflammasome and IL-1β Production
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DOI：
10.4049/jimmunol.1200312
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发表时间：
2012-10-15
影响因子：
4.4
通讯作者：
Masters, Seth L.
中科院分区：
文献类型：
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作者：
Haneklaus, Moritz;Gerlic, Motti;Masters, Seth L.
尽管TLR信号传导的microRNA（miRNA）调节已经很好地建立，但尚未观察到NLR蛋白或它们形成的炎性小体。我们现在已经验证了NLRP 3 3 '非翻译区中高度保守的miR-223靶位点。随着单核细胞分化为巨噬细胞，miR-223表达降低，而NLRP 3蛋白在此期间增加。然而，miR-223的过表达阻止NLRP 3蛋白的积累并抑制炎性小体产生IL-1 β。炎性体的病毒抑制是一个新兴的主题，我们还鉴定了可以靶向NLRP 3 3 '非翻译区中的miR-223结合位点的EBV miRNA。此外，该病毒miRNA可以通过外泌体从感染的B细胞分泌，以抑制未感染细胞中的NLRP 3炎性体。因此，我们已经鉴定了在骨髓细胞发育期间限制NLRP 3炎症能力的第一个内源性miRNA，以及利用这一点限制炎症的病毒miRNA。免疫学杂志，2012，189：3795-3799。
Although microRNA (miRNA) regulation of TLR signaling is well established, this has not yet been observed for NLR proteins or the inflammasomes they form. We have now validated a highly conserved miR-223 target site in the NLRP3 3'-untranslated region. miR-223 expression decreases as monocytes differentiate into macrophages, whereas NLRP3 protein increases during this time. However, overexpression of miR-223 prevents accumulation of NLRP3 protein and inhibits IL-1 beta production from the inflammasome. Virus inhibition of the inflammasome is an emerging theme, and we have also identified an EBV miRNA that can target the miR-223 binding site in the NLRP3 3'-untranslated region. Furthermore, this virus miRNA can be secreted from infected B cells via exosomes to inhibit the NLRP3 inflammasome in noninfected cells. Therefore, we have identified both the first endogenous miRNA that limits NLRP3 inflammatory capacity during myeloid cell development and also a viral miRNA that takes advantage of this, limiting inflammation for its own purposes. The Journal of Immunology, 2012, 189: 3795-3799.