Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) positively regulates lipopolysaccharide-induced expression of CXC chemokine ligand 10 and 11 in mouse macrophages

Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) positively regulates lipopolysaccharide-induced expression of CXC chemokine ligand 10 and 11 in mouse macrophages
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DOI:
10.1016/j.bbrc.2022.10.048
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发表时间:
2022-10-22
影响因子:
3.1
通讯作者:
Garlick,Jonathan
Garlick,Jonathan
中科院分区:
生物学4区
文献类型:
--
作者:
Bandow,Kenjiro;Smith,Avi;Garlick,Jonathan

文献摘要

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TREM2(骨髓细胞表达触发受体 2)是 Nasu-Hakola 病的致病基因,该病的特点是多发性骨囊肿和白质脑病。此外,还发现该基因的突变与阿尔茨海默病的发病有关。 TREM2 是一种在树突状细胞、小胶质细胞、破骨细胞和巨噬细胞上表达的免疫受体。细胞膜上的 TREM2 被一些蛋白酶脱落并以可溶性 TREM2 (sTREM2) 的形式释放。同时,已经报道了几种TREM2配体,脂多糖(LPS)是候选配体之一。使用 RNA 干扰检查巨噬细胞中 TREM2 介导的 LPS 反应,我们鉴定了五种趋化因子,其表达是通过 TREM2 诱导的。此外,我们还发现,LPS 诱导的 CXC 基序趋化因子配体 (Cxcl10) 和 Cxcl11 在五种趋化因子中的表达部分是通过 sTREM2 介导的。这些结果表明 sTREM2 在巨噬细胞中具有细胞因子样功能。
TREM2 (Triggering receptor expressed on myeloid cells 2) is the causative gene for Nasu-Hakola disease, which is characterized by multiple bone cysts and leukoencephalopathy. In addition, mutations in this gene have been found to be correlated with the onset of Alzheimer's disease. TREM2 is an immunoreceptor expressed on dendritic cells, microglia, osteoclasts, and macrophages. TREM2 on the cell membrane is shed by some proteases and released as soluble TREM2 (sTREM2). Meanwhile, several TREM2 ligands have been reported, and lipopolysaccharide (LPS) is one of the candidates. Using RNA interference to examine TREM2-mediated LPS response in macrophages, we identified five chemokines whose expression was induced via TREM2. Furthermore, we showed that LPS-induced expression ofCXC-motif chemokine ligand(Cxcl10) andCxcl11among the five chemokines was mediated in part through sTREM2. These results suggest that sTREM2 has cytokine-like functions in macrophages.