Evidence map›Paper›PMID 40482033›Full record

ArticleCell reports2025

The glycolytic reaction PGAM restrains Th17 pathogenicity and Th17-dependent autoimmunity.

Chao Wang, Allon Wagner, Johannes Fessler, David DeTomaso, Sarah Zaghouani, Yulin Zhou, Kerry Pierce, Raymond A Sobel, Clary Clish, Nir Yosef and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. ODC1 restricts meningeal B cell age-associated-like phenotype and function in multiple sclerosis: A human and experimental study.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Chao WangBiological Sciences Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: chao.wang@sri.utoronto.ca.
Allon WagnerDepartment of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Johannes FesslerDivision of Immunology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria.
David DeTomasoCenter for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Sarah ZaghouaniThe Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital and Harvard Medical School, Boston, MA 02115, USA.
Yulin ZhouBiological Sciences Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Kerry PierceBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Raymond A SobelPalo Alto Veteran's Administration Health Care System and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Clary ClishBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nir YosefDepartment of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: nir.yosef@weizmann.ac.il.
Vijay K KuchrooThe Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital and Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: vkuchroo@bwh.harvard.edu.

Funding

Tool and Technology Development CoreU19MH114821 · NIMH · COLD SPRING HARBOR LABORATORY · PI HUANG, Z JOSH · 2017 to 2021
$64.5M
Role of Negative Costimulation in Regulation of AutoimmunityP01AI039671 · NIAID · YALE UNIVERSITY · PI David A. Hafler · 1996 to 2026
$51.7M
Transgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI BLAZAR, BRUCE R · 2003 to 2023
$42.5M
Transgenic / Knock-out mouse coreP01AI073748 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI KUCHROO, VIJAY K. · 2008 to 2019
$17.1M
Role of Th1 specific cell surface molecule Tim-3 in EAE.R01NS045937 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KUCHROO, VIJAY K. · 2003 to 2016
$4.9M
T CELL RESPONSE TO MYELIN PROTEOLIPID PROTEINR01NS030843 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KUCHROO, VIJAY K. · 1998 to 2019
$4.1M
Role of Tim-3:Bat-3 pathway in inducing tolerogenic DCs and peripheral toleranceR01AI144166 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI VIJAY K. KUCHROO · 2020 to 2026
$3.2M
Metabolic regulators of Treg/Th17 balance in CNS autoimmunityR01AI169075 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI VIJAY K. KUCHROO · 2022 to 2026
$2.8M
Role of metabolic crosstalk in determining immunity during tumor progressionR01CA282794 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ANA C ANDERSON, VIJAY K. KUCHROO · 2023 to 2026
$2.0M
NCI NIH HHS R01 CA282794NIAID NIH HHS P01 AI039671NIAID NIH HHS P01 AI056299NIAID NIH HHS P01 AI073748NIAID NIH HHS R01 AI144166NIAID NIH HHS R01 AI169075NIMH NIH HHS U19 MH114821NINDS NIH HHS R01 NS030843NINDS NIH HHS R01 NS045937
6 · The paper itself

Abstract

Glucose metabolism is a critical regulator of T cell function, largely thought to support their activation and effector differentiation. Here, we investigate how individual glycolytic reactions determine the pathogenicity of T helper 17 (Th17) cells using Compass, an algorithm we previously developed for inferring metabolic states from single-cell RNA sequencing. Surprisingly, Compass predicted that the metabolic shunt between 3-phosphoglycerate (3PG) and 2-phosphoglycerate (2PG) is inversely correlated with pathogenicity in Th17 cells. Indeed, perturbation of phosphoglycerate mutase (PGAM), the enzyme catalyzing 3PG to 2PG conversion, induces a pathogenic gene expression program by suppressing a gene module associated with the least pathogenic state of Th17 cells. Finally, PGAM inhibition in Th17 cells exacerbates neuroinflammation in the adoptive transfer model of experimental autoimmune encephalomyelitis, consistently with PGAM promoting the non-pathogenic phenotype of Th17 cells. Overall, our study identifies PGAM, contrary to other glycolytic enzymes, as a negative regulator of pathogenic Th17 cell differentiation.

Indexed as

AutoimmunityGlycolysisPhosphoglycerate MutaseTh17 CellsAnimalsCell DifferentiationEncephalomyelitis, Autoimmune, ExperimentalMiceMice, Inbred C57BLPhosphoglycerate Mutasecentral carbon metabolismCP: ImmunologyCP: MetabolismEGCGepigallocatechin-3-gallateglycolysisimmune metabolismimmunometabolismPGAMPGMphosphoglycerate mutaseT helper 17

Identifiers

PMID40482033
PMCPMC12443480

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.