Evidence map›Paper›PMID 39738812›Full record

ArticleThe Journal of experimental medicine2025

The phospholipid kinase PIKFYVE is essential for Th17 differentiation.

Douglas S Prado, Richard T Cattley, Andreza B Sonego, Parth Sutariya, Shuxian Wu, Mijoon Lee, William C Boggess, Mark J Shlomchik, William F Hawse

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
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

9 authors.

Douglas S PradoDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0003-4594-1851
Richard T CattleyDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0009-0006-1258-093X
Andreza B SonegoDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-1014-5380
Parth SutariyaDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0009-0006-7656-3733
Shuxian WuDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0009-0002-4077-3692
Mijoon LeeDepartment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA.ORCID 0000-0001-7432-0427
William C BoggessDepartment of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA.ORCID 0000-0002-9742-8657
Mark J ShlomchikDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-2152-0959
William F HawseDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-8371-3345

Funding

Defining how phospholipid signaling networks control Th17 differentiation and effector functionR01AI175111 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI William Francis Hawse · 2024 to 2026
$1.9M
NIAID NIH HHS R01 AI175111NIH HHS 1R01AI175111University of Pittsburgh
6 · The paper itself

Abstract

T helper 17 (Th17) cells are effector cells that mediate inflammatory responses to bacterial and fungal pathogens. While the cytokine signaling inputs required to generate Th17s are established, less is known about intracellular pathways that drive Th17 differentiation. Our previously published phosphoproteomic screen identifies that PIKFYVE, a lipid kinase that generates the phosphatidylinositol PtdIns(3,5)P2, is activated during Th17 differentiation. Herein, we discovered that PIKFYVE regulates kinase and transcription factor networks to promote Th17 differentiation. As a specific example, PtdIns(3,5)P2 directly stimulates mTORC1 kinase activity to promote cell division and differentiation pathways. Furthermore, PIKFYVE promotes STAT3 phosphorylation, which is required for Th17 differentiation. Chemical inhibition or CD4-specific deletion of PIKFYVE reduces Th17 differentiation and autoimmune pathology in the experimental autoimmune encephalomyelitis murine model of multiple sclerosis. Our findings identify molecular mechanisms by which PIKFYVE promotes Th17 differentiation and suggest that PIKFYVE is a potential therapeutic target in Th17-driven autoimmune diseases.

Indexed as

Cell DifferentiationEncephalomyelitis, Autoimmune, ExperimentalPhosphatidylinositol 3-KinasesSTAT3 Transcription FactorTh17 CellsAnimalsMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLPhosphorylationSignal TransductionMechanistic Target of Rapamycin Complex 1Phosphatidylinositol 3-KinasesPikfyve protein, mouseStat3 protein, mouseSTAT3 Transcription Factor

Identifiers

PMID39738812
PMCPMC11687391

What Socratic 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 Socratic graph.