Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) Interacts With Colony-Stimulating Factor 1 Receptor (CSF1R) but Is Not Necessary for CSF1/CSF1R-Mediated Microglial Survival.
Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) Interacts With Colony-Stimulating Factor 1 Receptor (CSF1R) but Is Not Necessary for CSF1/CSF1R-Mediated Microglial Survival.
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骨髓细胞 2 上表达的触发受体 (TREM2) 与集落刺激因子 1 受体 (CSF1R) 相互作用，但对于 CSF1/CSF1R 介导的小胶质细胞存活不是必需的
DOI：
10.3389/fimmu.2021.633796
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zheng H
中科院分区：
文献类型：
--
作者：
Cheng B;Li X;Dai K;Duan S;Rong Z;Chen Y;Lü L;Liu Z;Huang X;Xu H;Zhang YW;Zheng H
髓样细胞触发受体2（TREM 2）和集落刺激因子1受体（CSF 1 R）是小胶质细胞病变的重要分子，小胶质细胞病变以小胶质细胞功能障碍为特征，近年来被认为是神经系统疾病的神经病理学标志。TREM 2和CSF 1 R是主要在脑中的小胶质细胞中表达的受体，并调节小胶质细胞的活化和存活。他们被认为在物理上非常接近。然而，这些受体之间是否存在直接相互作用仍然是难以捉摸的。此外，TREM 2和CSF 1 R相互作用的生理作用和机制仍有待确定。在这里，我们发现TREM 2与CSF 1 R相互作用的基础上，免疫共沉淀测定。此外，我们发现CSF 1 R敲低显著降低了原代小胶质细胞的存活率，并增加了Trem 2 mRNA水平。相反，在Trem 2缺陷的小胶质细胞中，CSF 1 R表达增加。有趣的是，CSF 1 R的配体CSF 1的施用部分恢复了Trem 2缺陷型小胶质细胞在体外和体内的存活。此外，CSF 1改善Trem 2-/-; 5XFAD小鼠脑中的Aβ斑块沉积。这些发现提供了坚实的证据，表明TREM 2和CSF 1 R具有形成复合物并相互调节其表达的内在能力。这些发现还表明CSF 1在具有阿尔茨海默病（AD）高风险的携带TREM 2变体的患者中的治疗干预中的潜在作用。
Triggering receptor expressed on myeloid cells-2 (TREM2) and colony-stimulating factor 1 receptor (CSF1R) are crucial molecules for microgliopathy, which is characterized by microglia dysfunction and has recently been proposed as the neuropathological hallmark of neurological disorders. TREM2 and CSF1R are receptors expressed primarily in microglia in the brain and modulate microglial activation and survival. They are thought to be in close physical proximity. However, whether there is a direct interaction between these receptors remains elusive. Moreover, the physiological role and mechanism of the interaction of TREM2 and CSF1R remain to be determined. Here, we found that TREM2 interacted with CSF1R based on a co-immunoprecipitation assay. Additionally, we found that CSF1R knockdown significantly reduced the survival of primary microglia and increased the Trem2 mRNA level. In contrast, CSF1R expression was increased in Trem2-deficient microglia. Interestingly, administration of CSF1, the ligand of CSF1R, partially restored the survival of Trem2-deficient microglia in vitro and in vivo. Furthermore, CSF1 ameliorated Aβ plaques deposition in Trem2-/-; 5XFAD mouse brain. These findings provide solid evidence that TREM2 and CSF1R have intrinsic abilities to form complexes and mutually modulate their expression. These findings also indicate the potential role of CSF1 in therapeutic intervention in TREM2 variant-bearing patients with a high risk of Alzheimer’s disease (AD).
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DOI：
10.4049/jimmunol.1102836
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Otero K;Shinohara M;Zhao H;Cella M;Gilfillan S;Colucci A;Faccio R;Ross FP;Teitelbaum SL;Takayanagi H;Colonna M
通讯作者：
Colonna M
DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
DOI：
10.1084/jem.20142322
发表时间：
2015-03-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jay TR;Miller CM;Cheng PJ;Graham LC;Bemiller S;Broihier ML;Xu G;Margevicius D;Karlo JC;Sousa GL;Cotleur AC;Butovsky O;Bekris L;Staugaitis SM;Leverenz JB;Pimplikar SW;Landreth GE;Howell GR;Ransohoff RM;Lamb BT
通讯作者：
Lamb BT
影响因子：
7.3
作者：
Peng Q;Malhotra S;Torchia JA;Kerr WG;Coggeshall KM;Humphrey MB
通讯作者：
Humphrey MB
影响因子：
10.9
作者：
Cannarile MA;Weisser M;Jacob W;Jegg AM;Ries CH;Rüttinger D
通讯作者：
Rüttinger D