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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
Baoying Cheng, Xin Li, Kai Dai, Shengshun Duan, Zhouyi Rong, Yingmin Chen, Liangcheng Lü, Zhaoji Liu et al.. Frontiers in immunology, 2021-03-25
Topic: Inflammation, microglia and astrocytes
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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APA 7th
Cheng, B., Li, X., Dai, K., Duan, S., Rong, Z., Chen, Y., et al. (2021). 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. Frontiers in immunology. https://doi.org/10.3389/fimmu.2021.633796
Vancouver
Cheng B, Li X, Dai K, Duan S, Rong Z, Chen Y, et al. 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. Frontiers in immunology. 2021. doi:10.3389/fimmu.2021.633796. PMID: 33841415.
BibTeX
@article{cheng2021-33841415,
author = {Cheng, Baoying and Li, Xin and Dai, Kai and Duan, Shengshun and Rong, Zhouyi and Chen, Yingmin and Lü, Liangcheng and Liu, Zhaoji and others},
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}},
journal = {Frontiers in immunology},
year = {2021},
doi = {10.3389/fimmu.2021.633796},
pmid = {33841415},
url = {https://doi.org/10.3389/fimmu.2021.633796}
}
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Key findings
- 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.
- 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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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 23 of the 56 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in immunology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33841415) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 23 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 23 of the 56 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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