Evidence map›Paper›PMID 38697116›Full record

ArticleImmunity2024

A CTCF-binding site in the Mdm1-Il22-Ifng locus shapes cytokine expression profiles and plays a critical role in early Th1 cell fate specification.

Chunhong Liu, Hiroyuki Nagashima, Nilisha Fernando, Victor Bass, Jaanam Gopalakrishnan, Sadie Signorella, Will Montgomery, Ai Ing Lim, Oliver Harrison, Lauren Reich and 17 more

Abstract read
In one paragraph

Article in Immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 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

27 authors.

Chunhong LiuNeuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Hiroyuki NagashimaLymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Nilisha FernandoNeuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Victor BassNeuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jaanam GopalakrishnanNeuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Sadie SignorellaNeuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA; Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Will MontgomeryNeuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ai Ing LimMetaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Oliver HarrisonMetaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Lauren ReichNeuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Chen YaoLymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Hong-Wei SunBiodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Stephen R BrooksBiodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kan JiangBiodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Vijayaraj NagarajanNeuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Yongbing ZhaoLymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Seolkyoung JungLymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Rachael PhillipsLymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Yohei MikamiLymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Caleb A LareauBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Yuka KannoLymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Dragana JankovicImmunoparasitology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Martin J AryeeBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Aleksandra PękowskaDioscuri Center of Chromatin Biology and Epigenomics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Yasmine BelkaidMetaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
John O'SheaLymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Han-Yu ShihNeuro-Immune Regulome Unit, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: han-yu.shih@nih.gov.

Funding

Stat transcription factors in immunoregulation and autoimmune diseaseZIAAR041159 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI O'SHEA, JOHN · 2009 to 2025
$49.3M
Applying Bioinformatics to Research in Immune, Muscle, and Bone DiseasesZICAR041173 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI SUN, HONG-WEI · 2021 to 2025
$10.3M
Genomic regulation of immune response in neurodegeneration in miceZIAEY000569 · NEI · NATIONAL EYE INSTITUTE · PI SHIH, HAN-YU · 2020 to 2025
$10.0M
Flow Cytometry COREZICEY000457 · NEI · NATIONAL EYE INSTITUTE · PI CASPI, RACHEL R. · 2009 to 2025
$5.9M
Intramural NIH HHS ZIA EY000569
6 · The paper itself

Abstract

Cytokine expression during T cell differentiation is a highly regulated process that involves long-range promoter-enhancer and CTCF-CTCF contacts at cytokine loci. Here, we investigated the impact of dynamic chromatin loop formation within the topologically associating domain (TAD) in regulating the expression of interferon gamma (IFN-γ) and interleukin-22 (IL-22); these cytokine loci are closely located in the genome and are associated with complex enhancer landscapes, which are selectively active in type 1 and type 3 lymphocytes. In situ Hi-C analyses revealed inducible TADs that insulated Ifng and Il22 enhancers during Th1 cell differentiation. Targeted deletion of a 17 bp boundary motif of these TADs imbalanced Th1- and Th17-associated immunity, both in vitro and in vivo, upon Toxoplasma gondii infection. In contrast, this boundary element was dispensable for cytokine regulation in natural killer cells. Our findings suggest that precise cytokine regulation relies on lineage- and developmental stage-specific interactions of 3D chromatin architectures and enhancer landscapes.

Indexed as

CCCTC-Binding FactorCell DifferentiationInterferon-gammaInterleukin-22InterleukinsTh1 CellsAnimalsBinding SitesCell LineageChromatinCytokinesEnhancer Elements, GeneticGene Expression RegulationMiceMice, Inbred C57BLTh17 CellsCCCTC-Binding FactorChromatinCytokinesInterferon-gammaInterleukin-22InterleukinsCBSsCTCFHi-Cinterferon-gammainterleukin-22lymphocytic choriomeningitis virusnatural killer cellssuper-enhancersTh1Th17three-dimensionaltopologically associating domainsToxoplasma gondii

Identifiers

PMID38697116
PMCPMC11108081

What OpenQuestion holds

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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.