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INPP5D/SHIP1 regulates inflammasome activation in human microglia
Vicky Chou, Seeley B Fancher, Richard V Pearse, Hyo Lee, Matti Lam, Nicholas T Seyfried, David A Bennett, Phillip L De Jager et al.. bioRxiv : the preprint server for biology, 2023-02-26
Topic: Inflammation, microglia and astrocytes
Microglia and neuroinflammation are implicated in the development and progression of Alzheimer's disease (AD). To better understand microglia-mediated processes in AD, we studied the function of INPP5D/SHIP1, a gene linked to AD through GWAS. Immunostaining and single nucleus RNA sequencing confirmed that INPP5D expression in the adult human brain is largely restricted to microglia. Examination of prefrontal cortex across a large cohort revealed reduced full length INPP5D protein levels in AD patient brains compared to cognitively normal controls. The functional consequences of reduced INPP5D activity were evaluated in human induced pluripotent stem cell derived microglia (iMGLs), using both pharmacological inhibition of the phosphatase activity of INPP5D and genetic reduction in copy number. Unbiased transcriptional and proteomic profiling of iMGLs suggested an upregulation of innate immune signaling pathways, lower levels of scavenger receptors, and altered inflammasome signaling with INPP5D reduction. INPP5D inhibition induced the secretion of IL-1ß and IL-18, further implicating inflammasome activation. Inflammasome activation was confirmed through visualization of inflammasome formation through ASC immunostaining in INPP5D-inhibited iMGLs, increased cleaved caspase-1 and through rescue of elevated IL-1ß and IL-18 with caspase-1 and NLRP3 inhibitors. This work implicates INPP5D as a regulator of inflammasome signaling in human microglia.
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APA 7th
Chou, V., Fancher, S. B., Pearse, R. V., Lee, H., Lam, M., Seyfried, N. T., et al. (2023). INPP5D/SHIP1 regulates inflammasome activation in human microglia. bioRxiv : the preprint server for biology. https://doi.org/10.1101/2023.02.25.530025
Vancouver
Chou V, Fancher SB, Pearse RV, Lee H, Lam M, Seyfried NT, et al. INPP5D/SHIP1 regulates inflammasome activation in human microglia. bioRxiv : the preprint server for biology. 2023. doi:10.1101/2023.02.25.530025. PMID: 36865139.
BibTeX
@article{chou2023-36865139,
author = {Chou, Vicky and Fancher, Seeley B and Pearse, Richard V and Lee, Hyo and Lam, Matti and Seyfried, Nicholas T and Bennett, David A and De Jager, Phillip L and others},
title = {{INPP5D/SHIP1 regulates inflammasome activation in human microglia}},
journal = {bioRxiv : the preprint server for biology},
year = {2023},
doi = {10.1101/2023.02.25.530025},
pmid = {36865139},
url = {https://doi.org/10.1101/2023.02.25.530025}
}
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Key findings
- Examination of prefrontal cortex across a large cohort revealed reduced full length INPP5D protein levels in AD patient brains compared to cognitively normal controls.
Study details
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 23 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. 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 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 14 of the 60 points we could judge it on, which is 23 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv : the preprint server for biology) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 3 / 5 | 2023 — 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 36865139) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 14 / 60 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 14 of the 60 points we could judge it on is 23 out of 100. |
| Total | 23 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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