Evidence map›Paper›PMID 34607960›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Phospholipase Cγ2 regulates endocannabinoid and eicosanoid networks in innate immune cells.

Hui Jing, Alex Reed, Olesya A Ulanovskaya, Jan-Sebastian Grigoleit, Dylan M Herbst, Cassandra L Henry, Haoxin Li, Sabrina Barbas, Jason Germain, Kim Masuda and 1 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.4field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Comprehensive summary: the role of PBX1 in development and cancers.Frontiers in cell and developmental biology · 2024
    Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Phospholipase Cγ2 regulates endocannabinoid and eicosanoid networks in innate immune cells.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Hui JingDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.
Alex ReedDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.
Olesya A UlanovskayaLundbeck La Jolla Research Center, La Jolla, CA 92121.
Jan-Sebastian GrigoleitLundbeck La Jolla Research Center, La Jolla, CA 92121.
Dylan M HerbstLundbeck La Jolla Research Center, La Jolla, CA 92121.
Cassandra L HenryLundbeck La Jolla Research Center, La Jolla, CA 92121.
Haoxin LiDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.
Sabrina BarbasDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.
Jason GermainDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.
Kim MasudaDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.
Benjamin F CravattDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037; cravatt@scripps.edu.
Scripps Research Institute · USLa Jolla Alcohol Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human genetic studies have pointed to a prominent role for innate immunity and lipid pathways in immunological and neurodegenerative disorders. Our understanding of the composition and function of immunomodulatory lipid networks in innate immune cells, however, remains incomplete. Here, we show that phospholipase Cγ2 (PLCγ2 or PLCG2)-mutations in which are associated with autoinflammatory disorders and Alzheimer's disease-serves as a principal source of diacylglycerol (DAG) pools that are converted into a cascade of bioactive endocannabinoid and eicosanoid lipids by DAG lipase (DAGL) and monoacylglycerol lipase (MGLL) enzymes in innate immune cells. We show that this lipid network is tonically stimulated by disease-relevant human mutations in PLCγ2, as well as Fc receptor activation in primary human and mouse macrophages. Genetic disruption of PLCγ2 in mouse microglia suppressed DAGL/MGLL-mediated endocannabinoid-eicosanoid cross-talk and also caused widespread transcriptional and proteomic changes, including the reorganization of immune-relevant lipid pathways reflected in reductions in DAGLB and elevations in PLA2G4A. Despite these changes,

Indexed as

AnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticCD68 MoleculeCell LineChlorocebus aethiopsCOS CellsCytokinesDiglyceridesEicosanoidsEndocannabinoidsGroup IV Phospholipases A2HEK293 CellsHumansImmunity, InnateInflammationAntigens, CDAntigens, Differentiation, MyelomonocyticCD68 antigen, humanCD68 MoleculeCytokinesDAGLA protein, humanDAGLB protein, humanDiglyceridesEicosanoidsEndocannabinoidsGroup IV Phospholipases A2LipopolysaccharidesLipoprotein LipaseMGLL protein, humanMonoacylglycerol LipasesPhospholipase C gammaPla2g4a protein, mousePLCG2 protein, humanProstaglandinsReceptors, Fceicosanoidendocannabinoidimmunenervous systemphospholipase

Identifiers

PMID34607960
PMCPMC8522274
OpenAlexW3202846314

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.