Evidence map›Paper›PMID 38587077›Full record

ArticleJCI insight2024

Single-cell molecular signature of pathogenic T helper subsets in type 2-associated disorders in humans.

Pedro H Gazzinelli-Guimaraes, Brittany Dulek, Phillip Swanson, Justin Lack, Mario Roederer, Thomas B Nutman

Abstract read
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

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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

6 authors.

Pedro H Gazzinelli-GuimaraesLaboratory of Parasitic Diseases.
Brittany DulekIntegrated Data Science Services, and.
Phillip SwansonVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Justin LackIntegrated Data Science Services, and.
Mario RoedererVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Thomas B NutmanLaboratory of Parasitic Diseases.

Funding

Infectious Diseases Research Technologies Core - BethesdaZICAI001051 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2009 to 2025
$226.1M
Immunoregulation /Immune Recognition In Filarial/Nonfilarial Parasitic InfectionZIAAI000197 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NUTMAN, THOMAS · 2009 to 2025
$23.4M
Th2-associated responses and their control in parasitic helminth infections and related disordersZIAAI000805 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NUTMAN, THOMAS · 2009 to 2024
$4.4M
Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH
6 · The paper itself

Abstract

To unravel the heterogeneity and molecular signature of effector memory Th2 cells (Tem2), we analyzed 23 individuals' PBMCs of filaria-infected (Filaria+) and 24 healthy volunteers (Filaria-), with or without coincident house dust mite (HDM) allergic sensitization. Flow cytometry revealed 3 CD4+ Tem subsets - CCR4+CCR6+CRTH2- Tem17, CCR4+CCR6-CRTH2+ Tem2, and CCR6+CCR4+CRTH2+ Tem17.2 - markedly enriched in Filaria+ individuals. These subsets were sorted and analyzed by multiomic single-cell RNA immunoprofiling. SingleR-annotated Th2 cells from Tem2 and Tem17.2 cell subsets had features of pathogenic Th2 effector cells based on their transcriptional signatures, with downregulated CD27 and elevated expression levels of ITGA4, IL17RB, HPGDS, KLRB1, PTGDR2, IL9R, IL4, IL5, and IL13 genes. When the Filaria+ individuals were subdivided based on their allergic status, Tem2 cells in HDM+Filaria+ individuals showed an overall reduction in TCR diversity, suggesting the occurrence of antigen-driven clonal expansion. Moreover, HDM+Filaria+ individuals showed not only an expansion in the frequency of both Tem2 and Tem17.2 cell subsets, but also a change in their molecular program by overexpressing GATA3, IL17RB, CLRF2, and KLRB1, as well as increased antigen-induced IL-4, IL-5, and IL-13 production, suggesting that aeroallergens reshape the transcriptional and functional programming of Th2 cell subsets in human filarial infection toward a pathogenic immunophenotype.

Indexed as

HypersensitivityT-Lymphocyte SubsetsAllergensAnimalsHumansPyroglyphidaeTh2 CellsAllergensAdaptive immunityAllergyImmunologyInfectious diseaseTh2 response

Identifiers

PMID38587077
PMCPMC11128205

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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.