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Distinct Signaling Pathways Regulate TREM2 Phagocytic and NFκB Antagonistic Activities
Yao H, Coppola K, Schweig JE, Crawford F, Mullan M, Paris D.. Frontiers in cellular neuroscience, 2019-10-10
Topic: Brain proteins, microglia and lab models
Several genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) have been shown to increase the risk of developing Alzheimer's disease (AD) supporting a role of microglia and immune cells in the pathobiology of AD. We have employed an ectopic model of TREM2 and DAP12 expression in HEK293 cells to study selectively TREM2 dependent signaling and phagocytic functions and evaluated the effects of some of the TREM2 mutations associated with AD. We show that shedding of the TREM2 N-terminal domain does not affect the inhibition of NFκB activation induced by TREM2 while it completely blocks phagocytosis suggesting that TREM2 anti-inflammatory properties can be mediated by the TREM2 C-terminal fragment while the phagocytic activity requires the full-length receptor.
Key findings
- We have employed an ectopic model of TREM2 and DAP12 expression in HEK293 cells to study selectively TREM2 dependent signaling and phagocytic functions and evaluated the effects of some of the TREM2 mutations associated with AD.
- We show that shedding of the TREM2 N-terminal domain does not affect the inhibition of NFκB activation induced by TREM2 while it completely blocks phagocytosis suggesting that TREM2 anti-inflammatory properties can be mediated by the TREM2 C-terminal fragment while the phagocytic activity requires the full-length receptor.
- In addition, we confirm in that model that apolipoprotein E (APOE) is a ligand for TREM2 and triggers TREM2 signaling.
- In particular, we show that APOE4 stimulates spleen tyrosine kinase (SYK) activation more potently than APOE2 in a TREM2 dependent manner.
Why it matters
Using an engineered cell model, this study found that shedding of the TREM2 N-terminal domain blocked phagocytosis but did not affect TREM2's inhibition of NFkB activation. This is laboratory cell work on signaling and does not show a treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 46/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in cellular neuroscience) |
| Journal's citation record | 2 / 4 | Frontiers in Cellular Neuroscience: journal h-index 175 (OpenAlex, 2026-10-29) |
| 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 | 2 / 5 | 2019 — within 10 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 | 5 / 7 | Cited 110 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.2 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 3 / 6 | Cited 3.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 3 / 4 | Cited 57 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Daniel Paris: h-index 39 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | James A. Haley Veterans' Hospital: institution h-index 222 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31649511) |
| Free to read | 2 / 2 | Free to read |
| Total | 46 / 100 | — |
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Read the original
- DOI: 10.3389/fncel.2019.00457
- PubMed: 31649511
- Original source →
- Free full text: Frontiers in Cellular Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Yao, H., Coppola, K., Schweig, J. E., Crawford, F., Mullan, M., & Paris, D. (2019). Distinct Signaling Pathways Regulate TREM2 Phagocytic and NFκB Antagonistic Activities. Frontiers in cellular neuroscience. https://doi.org/10.3389/fncel.2019.00457
Vancouver
Yao H, Coppola K, Schweig JE, Crawford F, Mullan M, Paris D. Distinct Signaling Pathways Regulate TREM2 Phagocytic and NFκB Antagonistic Activities. Frontiers in cellular neuroscience. 2019. doi:10.3389/fncel.2019.00457. PMID: 31649511.
BibTeX
@article{yao2019-31649511,
author = {Yao, H. and Coppola, K. and Schweig, J. E. and Crawford, F. and Mullan, M. and Paris, D.},
title = {{Distinct Signaling Pathways Regulate TREM2 Phagocytic and NFκB Antagonistic Activities}},
journal = {Frontiers in cellular neuroscience},
year = {2019},
doi = {10.3389/fncel.2019.00457},
pmid = {31649511},
url = {https://doi.org/10.3389/fncel.2019.00457}
}
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