Evidence map›Paper›PMID 40804530›Full record

ArticleNature immunology2025

Circadian circuits control plasticity of group 3 innate lymphoid cells by sustaining epigenetic configuration of RORγt.

Bishan Bhattarai, Alina Ulezko Antonova, Jose L Fachi, Leone S Hopkins, Matthew V D McCullen, Ankita Saini, Sarah de Oliveira, Wandy L Beatty, Erik S Musiek, Vijay K Kuchroo and 3 more

Erratum issuedAbstract read
In one paragraph

Article in Nature immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. RORγtScience immunology · 2026
    Article
  7. Review
  8. Review
  9. Review
  10. Clock genes keep intestinal ILC3s ticking.Nature reviews. Immunology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Bishan BhattaraiDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0003-1263-8554
Alina Ulezko AntonovaDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Jose L FachiDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-1035-5193
Leone S HopkinsDepartment of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0009-0007-7902-779X
Matthew V D McCullenDepartment of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0001-9138-1483
Ankita SainiDepartment of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0009-0000-3694-495X
Sarah de OliveiraDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-9449-9740
Wandy L BeattyDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-0715-7361
Erik S MusiekDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-8873-0360
Vijay K KuchrooGene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Mass General Hospital and Harvard Medical School and Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7177-2110
Mitchell A LazarDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8653-1280
Eugene M OltzDepartment of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0000-0002-2513-7156
Marco ColonnaDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. mcolonna@wustl.edu.ORCID http://orcid.org/0000-0001-5222-4987

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
REV-ERB Nuclear Receptors in Circadian Rhythm and MetabolismR01DK045586 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL A. LAZAR · 1992 to 2026
$12.0M
REGULATION OF GENE EXPRESSION - SMALL INTESTINER01DK030292 · NIDDK · WASHINGTON UNIVERSITY · PI JEFFREY I GORDON, ANDREI L OSTERMAN · 1986 to 2026
$6.5M
CIS-REGULATORY CIRCUITS FOR ILC FUNCTION AND PLASTICITYR01AI134035 · NIAID · WASHINGTON UNIVERSITY · PI MARCO COLONNA, Eugene M Oltz · 2018 to 2026
$4.8M
Mucosal Immune Defense Mechanisms of the Urinary BladderR01DK132327 · NIDDK · WASHINGTON UNIVERSITY · PI MARCO COLONNA, SCOTT J. HULTGREN · 2023 to 2026
$2.5M
MICROBIOTA-DEPENDENT CONTROL OF CLOSTRIDIUM DIFFICILE: THE ROLE OF ACETATE AND IL-22 BINDING PROTEINR01DK126969 · NIDDK · WASHINGTON UNIVERSITY · PI COLONNA, MARCO · 2021 to 2024
$1.6M
Interdisciplinary Program in Microbe-Host BiologyT32AI165391 · NIAID · OHIO STATE UNIVERSITY · PI RAJENDAR K DEORA, Daniel J Wozniak · 2022 to 2026
$1.5M
Plasticity of Innate Lymphoid Cells: Mechanisms and Biological ImpactR01DK124699 · NIDDK · WASHINGTON UNIVERSITY · PI COLONNA, MARCO · 2020 to 2023
$1.4M
NCI NIH HHS P30 CA091842NIAID NIH HHS R01 AI134035NIAID NIH HHS T32 AI165391NIDDK NIH HHS R01 DK030292NIDDK NIH HHS R01 DK045586NIDDK NIH HHS R01 DK124699NIDDK NIH HHS R01 DK126969NIDDK NIH HHS R01 DK132327U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) 1R01DK126969
6 · The paper itself

Abstract

The gut experiences daily fluctuations in microbes and nutrients aligned with circadian rhythms that regulate nutrient absorption and immune function. Group 3 innate lymphoid cells (ILC3s) support gut homeostasis through interleukin-22 (IL-22) but can convert into interferon-γ-producing ILC1s. How circadian proteins control this plasticity remains unclear. Here we showed that the circadian proteins REV-ERBα and REV-ERBβ maintain ILC3 identity. Their combined deletion promoted ILC3-to-ILC1 conversion, reduced energy metabolism and IL-22 production, increased interferon-γ production, and heightened susceptibility to Citrobacter rodentium infection. Single-cell multiomics and gene editing revealed that REV-ERBα/REV-ERBβ deficiency upregulated the transcription factor NFIL3, which repressed the expression of RORγt via a -2-kb cis-regulatory element in the Rorc gene, shifting cells toward a T-bet-driven state. Chromatin and metabolic analyses indicated that REV-ERBα/REV-ERBβ loss reprogrammed regulatory and metabolic circuits. Thus, REV-ERBα/REV-ERBβ safeguard gut integrity by regulating clock genes that control RORγt expression and preserve ILC3 identity and resistance to intestinal inflammation.

Indexed as

Circadian RhythmEpigenesis, GeneticImmunity, InnateLymphocytesNuclear Receptor Subfamily 1, Group F, Member 3AnimalsBasic-Leucine Zipper Transcription FactorsCell PlasticityCitrobacter rodentiumEnergy MetabolismEnterobacteriaceae InfectionsInterferon-gammaInterleukin-22InterleukinsMiceMice, Inbred C57BLBasic-Leucine Zipper Transcription FactorsInterferon-gammaInterleukin-22InterleukinsNfil3 protein, mouseNr1d1 protein, mouseNuclear Receptor Subfamily 1, Group D, Member 1Nuclear Receptor Subfamily 1, Group F, Member 3Rorc protein, mouse

Identifiers

PMID40804530
PMCPMC12633719

What OpenQuestion holds

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Registered trials

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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.