Evidence map›Paper›PMID 41888408›Full record

ArticleCellular and molecular life sciences : CMLS2026

STAT4 drives optimal expansion and transcriptional repression of type I interferon pathway in inflammatory ILC2.

Giuseppe Pietropaolo, Gianluca Scarno, Arianna Maria Candelotti, Giordana Garzillo, Chiara Di Censo, Giovanna Peruzzi, Cinzia Fionda, Helena Stabile, Francesca Sozio, Chiara D'Aquino and 17 more

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In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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.

Giuseppe PietropaoloDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Gianluca ScarnoHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Arianna Maria CandelottiDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Giordana GarzilloDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Chiara Di CensoDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Giovanna PeruzziCenter for Life Nano- & Neuro-Science, Istituto Italiano Di Tecnologia, Rome, Italy.
Cinzia FiondaDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Helena StabileDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Francesca SozioDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Chiara D'AquinoDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Rosa MolfettaDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Fabrizio LeoneDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00161, Rome, Italy.
Bianca Laura CinicolaDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00161, Rome, Italy.
Alessandra GoriDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00161, Rome, Italy.
Cecilia CiancagliniInnate Lymphoid Cells Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Silvia SantopoloInnate Lymphoid Cells Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Linda QuatriniInnate Lymphoid Cells Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Anna Maria ZicariDepartment of Maternal Infantile and Urological Sciences, Sapienza University of Rome, 00161, Rome, Italy.
Han-Yu ShihNeuro-Immune Regulome Unit, National Eye Institute, NIH, Bethesda, MD, USA.
Yohei MikamiDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Angela GismondiDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Giovanni BernardiniDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Katharine C HsuHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Angela SantoniDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Silvano SozzaniDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Mattia Laffranchi *Department of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy. mattia.laffranchi@uniroma1.it.
Giuseppe Sciumè *Department of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy. giuseppe.sciume@uniroma1.it.ORCID http://orcid.org/0000-0003-0131-512X

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Innate immune cells respond rapidly to environmental cues through signal-regulated transcription factors (SRTFs) that sense changes in the tissue microenvironment. Signal transducer and activator of transcription (STAT) proteins are critical regulators of cytokine signaling and determine polarized immune responses. Herein, we reveal that activated type 2 innate lymphocytes (ILC2s) express STAT4, a SRTF canonically linked to type 1 immunity. STAT4 expression is induced in ILC2s upon activation by the alarmin IL-25 and linked with accumulation of lung inflammatory ILC2s (iILC2s). Despite elevated STAT4 expression, iILC2s do not acquire type 1 features, such as interferon (IFN)-γ production or T-bet expression and do not respond to IL-12 stimulation. Instead, STAT4 is activated by type I IFNs and supports the maintenance of the iILC2 pool. Transcriptomic analysis of Stat4-deficient ILC2s reveals enhanced type I IFN signaling and impaired proliferation, suggesting that STAT4 functions to antagonize IFN-driven suppression. Our data uncover a novel regulatory axis in which IL-25-induced STAT4 expression equips ILC2s to modulate interferon responses and to prevent aberrant autocrine function of type I IFNs, thus sustaining inflammatory effector populations during immune activation. These findings broaden the understanding of ILC2 activation and suggest new avenues for modulating innate lymphocytes in inflammatory diseases.

Indexed as

Immunity, InnateInflammationInterferon Type ILymphocytesSTAT4 Transcription FactorAnimalsInterferon-gammaMiceMice, Inbred C57BLSignal TransductionInterferon-gammaInterferon Type IStat4 protein, mouseSTAT4 Transcription FactorCytokinesInnate lymphoid cellsInterferonsJAK/STAT pathwayTranscriptional regulation

Identifiers

PMID41888408
PMCPMC13049133

What OpenQuestion holds

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LicenceCC BY
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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.