Evidence map›Paper›PMID 39317186›Full record

ArticleCell metabolism2024

IL-22 resolves MASLD via enterocyte STAT3 restoration of diet-perturbed intestinal homeostasis.

Peng Zhang, Junlai Liu, Allen Lee, Irene Tsaur, Masafumi Ohira, Vivian Duong, Nicholas Vo, Kosuke Watari, Hua Su, Ju Youn Kim and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
–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

32 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  4. Article
  5. Review
  6. Microorganisms · 2026
    Article
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  16. IL-1β-induced STAT3 activation drives IL-17-producing CD8Journal of translational medicine · 2025
    Article
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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

25 authors.

Peng ZhangLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Junlai LiuLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Allen LeeLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Irene TsaurLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Masafumi OhiraLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Vivian DuongLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Nicholas VoLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Kosuke WatariLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Hua SuLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Ju Youn KimLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Li GuLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Mandy ZhuLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Shabnam ShalapourDepartment of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mojgan HosseiniDepartment of Pathology, University of California, San Diego, San Diego, CA, USA.
Gautam BandyopadhyayDivision of Endocrinology & Metabolism, University of California, San Diego, San Diego, CA, USA.
Suling ZengDepartment of Medicine, University of California, San Diego, San Diego, CA, USA.
Cristina LlorenteDepartment of Medicine, University of California, San Diego, San Diego, CA, USA.
Haoqi Nina ZhaoSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA.
Santosh LamichhaneSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA; Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.
Siddharth MohanSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA.
Pieter C DorresteinSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA.
Jerrold M OlefskyDivision of Endocrinology & Metabolism, University of California, San Diego, San Diego, CA, USA.
Bernd SchnablDepartment of Medicine, University of California, San Diego, San Diego, CA, USA.
Pejman SorooshJanssen Research & Development, San Diego, CA 92121, USA.
Michael KarinLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: karinoffice@ucsd.edu.

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
NF-kappaB and Mitochondrial Signals as Positive and Negative Regulators of InflammationR37AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin · 2018 to 2026
$6.0M
Resource-based Center for the study of the joint microenvironment in rheumatology (Overall Application)P30AR073761 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CORR, MARY P · 2018 to 2022
$3.9M
The NRF2-FBP1 crossregulatory loop and the control of healthy and diseased liver metabolismR01DK133448 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin, Jun Hee Lee · 2022 to 2026
$3.6M
Microbiome and Intestinal Innate Immune Response in Alcoholic Liver DiseaseR37AA020703 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2021 to 2026
$2.5M
Goblet cells and intestinal immune response in alcohol-associated liver diseaseR01AA029106 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Ana Cristina Llorente Izquierdo · 2022 to 2026
$2.3M
Effects of early life Triclosan exposure through lactation on the gut-liver axis and its implications in the development of steatotic liver disease in adultsR01ES036571 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin, Robert H Tukey · 2025 to 2026
$1.5M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
The role of intestinal gp130 in alcohol-associated liver diseaseR21AA030654 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LLORENTE IZQUIERDO, ANA CRISTINA · 2023 to 2023
$415k
10X Chromium Connect for Single Cell Library Preparations for Translational ResearchS10OD032398 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VARNER, JUDITH A · 2022 to 2022
$284k
NCI NIH HHS P30 CA023100NIAAA NIH HHS R01 AA029106NIAAA NIH HHS R21 AA030654NIAAA NIH HHS R37 AA020703NIAID NIH HHS R37 AI043477NIAMS NIH HHS P30 AR073761NIDDK NIH HHS P30 DK120515NIDDK NIH HHS R01 DK133448NIEHS NIH HHS R01 ES036571NIH HHS S10 OD026929NIH HHS S10 OD032398NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

The exponential rise in metabolic dysfunction-associated steatotic liver disease (MASLD) parallels the ever-increasing consumption of energy-dense diets, underscoring the need for effective MASLD-resolving drugs. MASLD pathogenesis is linked to obesity, diabetes, "gut-liver axis" alterations, and defective interleukin-22 (IL-22) signaling. Although barrier-protective IL-22 blunts diet-induced metabolic alterations, inhibits lipid intake, and reverses microbial dysbiosis, obesogenic diets rapidly suppress its production by small intestine-localized innate lymphocytes. This results in STAT3 inhibition in intestinal epithelial cells (IECs) and expansion of the absorptive enterocyte compartment. These MASLD-sustaining aberrations were reversed by administration of recombinant IL-22, which resolved hepatosteatosis, inflammation, fibrosis, and insulin resistance. Exogenous IL-22 exerted its therapeutic effects through its IEC receptor, rather than hepatocytes, activating STAT3 and inhibiting WNT-β-catenin signaling to shrink the absorptive enterocyte compartment. By reversing diet-reinforced macronutrient absorption, the main source of liver lipids, IL-22 signaling restoration represents a potentially effective interception of dietary obesity and MASLD.

Indexed as

EnterocytesInterleukin-22STAT3 Transcription FactorAnimalsDietDiet, High-FatFatty LiverHomeostasisHumansInterleukinsIntestinal MucosaIntestinesMaleMiceMice, Inbred C57BLInterleukin-22InterleukinsStat3 protein, mouseSTAT3 Transcription FactorhepatosteatosisIL-22lipid absorptionMASLDSTAT3WNT-β-catenin

Identifiers

PMID39317186
PMCPMC11631175

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.