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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) 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 CS...

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Autores principales: Cheng, Baoying, Li, Xin, Dai, Kai, Duan, Shengshun, Rong, Zhouyi, Chen, Yingmin, Lü, Liangcheng, Liu, Zhaoji, Huang, Xiaohua, Xu, Huaxi, Zhang, Yun-Wu, Zheng, Honghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027073/
https://www.ncbi.nlm.nih.gov/pubmed/33841415
http://dx.doi.org/10.3389/fimmu.2021.633796
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author Cheng, Baoying
Li, Xin
Dai, Kai
Duan, Shengshun
Rong, Zhouyi
Chen, Yingmin
Lü, Liangcheng
Liu, Zhaoji
Huang, Xiaohua
Xu, Huaxi
Zhang, Yun-Wu
Zheng, Honghua
author_facet Cheng, Baoying
Li, Xin
Dai, Kai
Duan, Shengshun
Rong, Zhouyi
Chen, Yingmin
Lü, Liangcheng
Liu, Zhaoji
Huang, Xiaohua
Xu, Huaxi
Zhang, Yun-Wu
Zheng, Honghua
author_sort Cheng, Baoying
collection PubMed
description 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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spelling pubmed-80270732021-04-09 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 Cheng, Baoying Li, Xin Dai, Kai Duan, Shengshun Rong, Zhouyi Chen, Yingmin Lü, Liangcheng Liu, Zhaoji Huang, Xiaohua Xu, Huaxi Zhang, Yun-Wu Zheng, Honghua Front Immunol Immunology 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). Frontiers Media S.A. 2021-03-25 /pmc/articles/PMC8027073/ /pubmed/33841415 http://dx.doi.org/10.3389/fimmu.2021.633796 Text en Copyright © 2021 Cheng, Li, Dai, Duan, Rong, Chen, Lü, Liu, Huang, Xu, Zhang and Zheng https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Cheng, Baoying
Li, Xin
Dai, Kai
Duan, Shengshun
Rong, Zhouyi
Chen, Yingmin
Lü, Liangcheng
Liu, Zhaoji
Huang, Xiaohua
Xu, Huaxi
Zhang, Yun-Wu
Zheng, Honghua
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027073/
https://www.ncbi.nlm.nih.gov/pubmed/33841415
http://dx.doi.org/10.3389/fimmu.2021.633796
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