Evidence map›Paper›PMID 34559433›Full record

ArticleGlia2022

Tumor necrosis factor receptor-1 is selectively sequestered into Schwann cell extracellular vesicles where it functions as a TNFα decoy.

Mahrou Sadri, Naoya Hirosawa, Jasmine Le, Haylie Romero, Stefano Martellucci, Hyo Jun Kwon, Donald Pizzo, Seiji Ohtori, Steven L Gonias, Wendy M Campana

Open access · greenAbstract read
In one paragraph

Article in Glia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Effects of photobiomodulation on nociceptor activity and the expression of proinflammatory cytokines after temporomandibular joint disc injury in rats.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026
    Article
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  4. Review
  5. Review
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  9. Article
  10. α1-Antitrypsin derived SP16 peptide demonstrates efficacy in rodent models of acute and neuropathic pain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    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

10 authors at 2 institutions in 2 countries.

Mahrou SadriDepartment of Anesthesiology, University of California, San Diego, La Jolla, California, USA.
Naoya HirosawaDepartment of Anesthesiology, University of California, San Diego, La Jolla, California, USA.
Jasmine LeDepartment of Anesthesiology, University of California, San Diego, La Jolla, California, USA.ORCID 0000-0002-8521-765X
Haylie RomeroDepartment of Anesthesiology, University of California, San Diego, La Jolla, California, USA.
Stefano MartellucciDepartment of Anesthesiology, University of California, San Diego, La Jolla, California, USA.ORCID 0000-0002-3952-3162
Hyo Jun KwonDepartment of Anesthesiology, University of California, San Diego, La Jolla, California, USA.
Donald PizzoDepartment of Pathology, University of California, San Diego, California, USA.
Seiji OhtoriDepartment of Orthopaedic Surgery and Graduate School in Medicine, Chiba University, Chiba, Japan.
Steven L GoniasDepartment of Pathology, University of California, San Diego, California, USA.
Wendy M CampanaDepartment of Anesthesiology, University of California, San Diego, La Jolla, California, USA.ORCID 0000-0002-9039-1396
University of California San Diego · USChiba University · JP

Funding

Neurosciences Graduate Training ProgramT32NS061847 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Brenda L Bloodgood · 2008 to 2026
$7.7M
Schwann Cell NMDA Receptor in PNS InjuryR01NS097590 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CAMPANA, WENDY M., GONIAS, STEVEN L. · 2017 to 2020
$1.4M
Targeting Schwann cell exosomes for treating neuropathic painI01RX003363 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI CAMPANA, WENDY M. · 2020 to 2023
–
NINDS NIH HHS R01 NS097590NINDS NIH HHS T32 NS061847RRD VA I01 RX002484RRD VA I01 RX003363
6 · The paper itself

Abstract

Schwann cells (SCs) are known to produce extracellular vesicles (EV) that participate in cell-cell communication by transferring cargo to target cells, including mRNAs, microRNAs, and biologically active proteins. Herein, we report a novel mechanism whereby SC EVs may regulate PNS physiology, especially in injury, by controlling the activity of TNFα. SCs actively sequester tumor necrosis factor receptor-1 (TNFR1) into EVs at high density, accounting for about 2% of the total protein in SC EVs (~1000 copies TNFR1/EV). Although TNFR2 was robustly expressed by SCs in culture, TNFR2 was excluded from SC EVs. SC EV TNFR1 bound TNFα, decreasing the concentration of free TNFα available to bind to cells and thus served as a TNFα decoy. SC EV TNFR1 significantly inhibited TNFα-induced p38 MAPK phosphorylation in cultured SCs. When TNFR1 was proteolytically removed from SC EVs using tumor necrosis factor-α converting enzyme (TACE) or neutralized with antibody, the ability of TNFα to activate p38 MAPK in the presence of these EVs was restored. As further evidence of its decoy activity, SC EV TNFR1 modified TNFα activities in vitro including: (1) regulation of expression of other cytokines; (2) effects on SC morphology; and (3) effects on SC viability. SC EVs also modified the effects of TNFα on sciatic nerve morphology and neuropathic pain-related behavior in vivo. By sequestering TNFR1 in EVs, SCs may buffer against the potentially toxic effects of TNFα. SC EVs provide a novel mechanism for the spatial and temporal regulation of neuro-inflammation.

Indexed as

Extracellular VesiclesReceptors, Tumor Necrosis Factor, Type ISchwann CellsTumor Necrosis Factor-alphaCells, CulturedReceptors, Tumor Necrosis Factor, Type IIReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IITumor Necrosis Factor-alphaextracellular vesiclesneuropathic painperipheral nerve injurySchwann cellsTNF Receptor-1TNFα

Identifiers

PMID34559433
PMCPMC10656730
OpenAlexW3201173542

What OpenQuestion holds

Textmetadata
LicenceTDM
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.