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Record W2912908416 · doi:10.1084/jem.20180722

Self-reactive CD4+ IL-3+ T cells amplify autoimmune inflammation in myocarditis by inciting monocyte chemotaxis

2019· article· en· W2912908416 on OpenAlexfundno aff
Atsushi Anzai, John E. Mindur, Lennard Halle, Soichi Sano, Jennifer L. Choi, Shun He, Cameron S. McAlpine, Christopher T. Chan, Florian Kahles, Colin Valet, Ashley M. Fenn, Manfred Nairz, Sara Rattik, Yoshiko Iwamoto, DeLisa Fairweather, Kenneth Walsh, Peter Libby, Matthias Nahrendorf, Filip K. Świrski

Bibliographic record

VenueThe Journal of Experimental Medicine · 2019
Typearticle
Languageen
FieldMedicine
TopicViral Infections and Immunology Research
Canadian institutionsnot available
FundersNational Heart, Lung, and Blood InstituteJapan Society for the Promotion of ScienceFondation pour la Recherche MédicaleNational Institutes of HealthKeio UniversityAmerican Heart AssociationCanadian Institutes of Health ResearchUehara Memorial FoundationNational Institute of Environmental Health SciencesKanae Foundation for the Promotion of Medical ScienceMassachusetts General HospitalHarvard Stem Cell InstituteBanting Research Foundation
KeywordsInflammationMyocarditisImmunologyChemokineEffectorMonocyteChemotaxisT cellMedicineImmune systemBiologyReceptorInternal medicine

Abstract

fetched live from OpenAlex

Acquisition of self-reactive effector CD4+ T cells is a major component of the autoimmune response that can occur during myocarditis, an inflammatory form of cardiomyopathy. Although the processes by which self-reactive T cells gain effector function have received considerable attention, how these T cells contribute to effector organ inflammation and damage is less clear. Here, we identified an IL-3–dependent amplification loop that exacerbates autoimmune inflammation. In experimental myocarditis, we show that effector organ–accumulating autoreactive IL-3+ CD4+ T cells stimulate IL-3R+ tissue macrophages to produce monocyte-attracting chemokines. The newly recruited monocytes differentiate into antigen-presenting cells that stimulate local IL-3+ CD4+ T cell proliferation, thereby amplifying organ inflammation. Consequently, Il3−/− mice resist developing robust autoimmune inflammation and myocardial dysfunction, whereas therapeutic IL-3 targeting ameliorates disease. This study defines a mechanism that orchestrates inflammation in myocarditis, describes a previously unknown function for IL-3, and identifies IL-3 as a potential therapeutic target in patients with myocarditis.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.032
Threshold uncertainty score0.435

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.300
Teacher spread0.288 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations56
Published2019
Admission routes1
Has abstractyes

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