Evidence map›Paper›PMID 29618665›Full record

ArticleJCI insight2018

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex.

Caroline H Wallace, Bill X Wu, Mohammad Salem, Ephraim A Ansa-Addo, Alessandra Metelli, Shaoli Sun, Gary Gilkeson, Mark J Shlomchik, Bei Liu, Zihai Li

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.1field-weighted citation impact, top 10% 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

34 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
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  4. Blunting specific T-dependent antibody responses with engineered "decoy" B cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
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  16. Journal of asthma and allergy · 2022
    Article
  17. Review
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  19. Article
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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 4 institutions in 2 countries.

Caroline H WallaceDepartment of Microbiology and Immunology.
Bill X WuDepartment of Microbiology and Immunology.
Mohammad SalemDepartment of Microbiology and Immunology.
Ephraim A Ansa-AddoDepartment of Microbiology and Immunology.
Alessandra MetelliDepartment of Microbiology and Immunology.
Shaoli SunDepartment of Pathology and Laboratory Medicine, and.
Gary GilkesonDepartment of Microbiology and Immunology.
Mark J ShlomchikDepartment of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Bei LiuDepartment of Microbiology and Immunology.
Zihai LiDepartment of Microbiology and Immunology.
Emory University Hospital · USFirst Affiliated Hospital of Zhengzhou University · CNMedical University of South Carolina · USUniversity of Pittsburgh · US

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Jian Ouyang · 2009 to 2026
$42.7M
South Carolina Clinical & Translational Research Institute (SCTR)UL1TR001450 · NCATS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BRADY, KATHLEEN T., FLUME, PATRICK A · 2015 to 2024
$41.1M
Project 3: Structural Basis for grp94 Drug Development and Chaperone FunctionP01CA186866 · NCI · OHIO STATE UNIVERSITY · PI GEWIRTH, DANIEL T · 2015 to 2019
$6.7M
Patient Resource CoreP60AR062755 · NIAMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI GILKESON, GARY S · 2012 to 2016
$5.8M
South Carolina Clinical & Translational Research Institute (SCTR)TL1TR001451 · NCATS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI FEGHALI-BOSTWICK, CAROL A. · 2015 to 2024
$4.6M
Molecular chaperones and immune toleranceR01AI077283 · NIAID · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI LI, ZIHAI · 2009 to 2021
$3.7M
Extrinsic and intrinsic factors regulating commensal-specific T helper-17 cellsU01AI125859 · NIAID · OHIO STATE UNIVERSITY · PI LIU, BEI · 2016 to 2020
$2.5M
Thrombocytes in Cancer ImmunityR01CA188419 · NCI · OHIO STATE UNIVERSITY · PI LI, ZIHAI · 2015 to 2019
$1.9M
Mechanism of gp96/grp94 in regulating plasma cells and myelomaR01CA193939 · NCI · OHIO STATE UNIVERSITY · PI LIU, BEI · 2016 to 2020
$1.7M
Integration of inflammation and cancer by molecular chaperoneR01CA213290 · NCI · OHIO STATE UNIVERSITY · PI LI, ZIHAI · 2017 to 2021
$860k
NCATS NIH HHS TL1 TR001451NCATS NIH HHS UL1 TR001450NCI NIH HHS P01 CA186866NCI NIH HHS P30 CA138313NCI NIH HHS R01 CA188419NCI NIH HHS R01 CA193939NCI NIH HHS R01 CA213290NIAID NIH HHS R01 AI077283NIAID NIH HHS U01 AI125859NIAMS NIH HHS P60 AR062755
6 · The paper itself

Abstract

GARP, a cell surface docking receptor for binding and activating latent TGF-β, is highly expressed by platelets and activated Tregs. While GARP is implicated in immune invasion in cancer, the roles of the GARP-TGF-β axis in systemic autoimmune diseases are unknown. Although B cells do not express GARP at baseline, we found that the GARP-TGF-β complex is induced on activated human and mouse B cells by ligands for multiple TLRs, including TLR4, TLR7, and TLR9. GARP overexpression on B cells inhibited their proliferation, induced IgA class-switching, and dampened T cell-independent antibody production. In contrast, B cell-specific deletion of GARP-encoding gene Lrrc32 in mice led to development of systemic autoimmune diseases spontaneously as well as worsening of pristane-induced lupus-like disease. Canonical TGF-β signaling more readily upregulates GARP in Peyer patch B cells than in splenic B cells. Furthermore, we demonstrated that B cells are required for the induction of oral tolerance of T cell-dependent antigens via GARP. Our studies reveal for the first time to our knowledge that cell surface GARP-TGF-β is an important checkpoint for regulating B cell peripheral tolerance, highlighting a mechanism of autoimmune disease pathogenesis.

Indexed as

Adjuvants, ImmunologicAnimalsAutoimmune DiseasesB-LymphocytesBone Marrow TransplantationCells, CulturedFemaleGene Knock-In TechniquesHealthy VolunteersHumansImmune ToleranceMembrane ProteinsMiceMice, TransgenicPrimary Cell CultureSignal TransductionAdjuvants, ImmunologicLRRC32 protein, humanLrrc32 protein, mouseMembrane ProteinsTransforming Growth Factor betaAutoimmunityB cellsImmunologyLupusTolerance

Identifiers

PMID29618665
PMCPMC5928869
OpenAlexW2795512202

What OpenQuestion holds

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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.