Evidence map›Paper›PMID 36115338›Full record

ArticleImmunity2022

The CD4

Thomas K Pedersen, Eric M Brown, Damian R Plichta, Joachim Johansen, Shaina W Twardus, Toni M Delorey, Helena Lau, Hera Vlamakis, James J Moon, Ramnik J Xavier and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
9.0field-weighted citation impact, top 2% 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

37 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
  2. Gut microbes · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. The danger theory of immunity revisited.Nature reviews. Immunology · 2024
    Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Thomas K PedersenInfectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Disease Systems Immunology, Department of Biotechnology and Biomedicine, Section for Protein Science and Biotherapeutics, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
Eric M BrownInfectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Damian R PlichtaInfectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Joachim JohansenInfectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Shaina W TwardusCenter for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Toni M DeloreyKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Helena LauCenter for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Hera VlamakisInfectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
James J MoonCenter for Immunology and Inflammatory Diseases and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Ramnik J XavierInfectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Center for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: xavier@molbio.mgh.harvard.edu.
Daniel B GrahamInfectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Center for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: dgraham@broadinstitute.org.
Broad Institute · USHarvard University · USMassachusetts General Hospital · USUniversity of Copenhagen · DK

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
The importance of the IgG4 glycome in IgG4-related disease(s)U19AI110495 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI SHIV Subramaniam PILLAI · 2014 to 2026
$7.9M
Determinants of inception of inflammation in inflammatory bowel diseasesR01DK127171 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI ANANTHAKRISHNAN, ASHWIN N, XAVIER, RAMNIK J · 2021 to 2025
$5.4M
ATG16L1 T300A: genetics to biologyR01DK097485 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI XAVIER, RAMNIK J · 2013 to 2021
$4.1M
Cardiovascular disease, metabolic syndrome, microbes and metabolites in FHSR01HL157717 · NHLBI · BROAD INSTITUTE, INC. · PI XAVIER, RAMNIK J · 2022 to 2025
$3.9M
T cell Tolerance to Enteric Commensal BacteriaR01DK126910 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MOON, JAMES J · 2021 to 2024
$2.0M
NHLBI NIH HHS R01 HL157717NIAID NIH HHS U19 AI110495NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK097485NIDDK NIH HHS R01 DK126910NIDDK NIH HHS R01 DK127171
6 · The paper itself

Abstract

Reciprocal interactions between host T helper cells and gut microbiota enforce local immunological tolerance and modulate extra-intestinal immunity. However, our understanding of antigen-specific tolerance to the microbiome is limited. Here, we developed a systematic approach to predict HLA class-II-specific epitopes using the humanized bacteria-originated T cell antigen (hBOTA) algorithm. We identified a diverse set of microbiome epitopes spanning all major taxa that are compatible with presentation by multiple HLA-II alleles. In particular, we uncovered an immunodominant epitope from the TonB-dependent receptor SusC that was universally recognized and ubiquitous among Bacteroidales. In healthy human subjects, SusC-reactive T cell responses were characterized by IL-10-dominant cytokine profiles, whereas in patients with active Crohn's disease, responses were associated with elevated IL-17A. Our results highlight the potential of targeted antigen discovery within the microbiome to reveal principles of tolerance and functional transitions during inflammation.

Indexed as

Crohn DiseaseImmunodominant EpitopesCD4-Positive T-LymphocytesEpitopes, T-LymphocyteHumansInterleukin-10Interleukin-17Epitopes, T-LymphocyteImmunodominant EpitopesInterleukin-10Interleukin-17epitope predictionimmunodominanceinflammationinflammatory bowel diseasemetagenomicsMHC class IImicrobial antigensmicrobiomemucosal immunologyT cells

Identifiers

PMID36115338
PMCPMC9890645
OpenAlexW4296067424

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.