Evidence map›Paper›PMID 34914635›Full record

ArticleJCI insight2022

The RNA-binding protein IMP2 drives a stromal-Th17 cell circuit in autoimmune neuroinflammation.

Rami Bechara, Nilesh Amatya, Saikat Majumder, Chunsheng Zhou, Yang Li, Qixing Liu, Mandy J McGeachy, Sarah L Gaffen

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Loss of ADAP1/CentA1 Protects Against Autoimmune Demyelination.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  5. IMPlications of IMP2 in RNA Biology and Disease.International journal of molecular sciences · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Post-transcriptional checkpoints in autoimmunity.Nature reviews. Rheumatology · 2023
    Review
  10. Article
  11. Review
  12. Article
  13. 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

8 authors at 2 institutions in 3 countries.

Rami BecharaUniversité Paris-Saclay, CEA, INSERM UMR 1184, Center for Research in Immunology of Viral, Autoimmune, Hematological and Bacterial Diseases (IMVA-HB), Le Kremlin Bicêtre, France.
Nilesh AmatyaDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Saikat MajumderDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Chunsheng ZhouDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Yang LiDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Qixing LiuDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Mandy J McGeachyDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Sarah L GaffenDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
University of Pittsburgh · USInserm · FR

Funding

Molecular Mechanisms of IL-17-dependent autoimmune signalingR01AI147383 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GAFFEN, SARAH L · 2020 to 2024
$2.6M
IL-17 regulates LN stromal cell metabolism and functionR01AI148356 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MCGEACHY, MANDY J · 2020 to 2023
$1.8M
NIAID NIH HHS R01 AI147383NIAID NIH HHS R01 AI148356
6 · The paper itself

Abstract

Stromal cells are emerging as key drivers of autoimmunity, partially because they produce inflammatory chemokines that orchestrate inflammation. Chemokine expression is regulated transcriptionally but also through posttranscriptional mechanisms, the specific drivers of which are still incompletely defined. CCL2 (MCP1) is a multifunctional chemokine that drives myeloid cell recruitment. During experimental autoimmune encephalomyelitis (EAE), an IL-17-driven model of multiple sclerosis, CCL2 produced by lymph node (LN) stromal cells was essential for immunopathology. Here, we showed that Ccl2 mRNA upregulation in human stromal fibroblasts in response to IL-17 required the RNA-binding protein IGF-2 mRNA-binding protein 2 (IGF2BP2, IMP2), which is expressed almost exclusively in nonhematopoietic cells. IMP2 binds directly to CCL2 mRNA, markedly extending its transcript half-life, and is thus required for efficient CCL2 secretion. Consistent with this, Imp2-/- mice showed reduced CCL2 production in LNs during EAE, causing impairments in monocyte recruitment and Th17 cell polarization. Imp2-/- mice were fully protected from CNS inflammation. Moreover, deletion of IMP2 after EAE onset was sufficient to mitigate disease severity. These data showed that posttranscriptional control of Ccl2 in stromal cells by IMP2 was required to permit IL-17-driven progression of EAE pathogenesis.

Indexed as

AutoimmunityGene Expression RegulationUp-RegulationAnimalsCells, CulturedEncephalomyelitis, Autoimmune, ExperimentalFemaleMaleMiceMice, Inbred C57BLRNA-Binding ProteinsRNA, MessengerTh17 CellsIGF2BP2 protein, mouseRNA-Binding ProteinsRNA, MessengerAutoimmunityChemokinesCytokinesImmunologySignal transduction

Identifiers

PMID34914635
PMCPMC8855811
OpenAlexW4200426374

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.