ArticleCellular and molecular gastroenterology and hepatology2022
Sex-Dependent Hepatoprotective Role of IL-22 Receptor Signaling in Non-Alcoholic Fatty Liver Disease-Related Fibrosis.
Article in Cellular and molecular gastroenterology and hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Collaborative functionality between three types of inflammation in idiopathic pulmonary fibrosis.Nature immunology · 2026Review
- Gut-liver axis molecular mechanisms in alcohol-associated liver disease.Alcohol (Fayetteville, N.Y.) · 2026Review
- DPP4 inhibition affects metabolism and inflammation associated pathways in hiPSC-derived steatotic HLCs.Frontiers in cell and developmental biology · 2026Article
- An Update on IL-22 Therapies in Alcohol-Associated Liver Disease and Beyond.The American journal of pathology · 2026Review
- Dual roles of T cells in metabolic dysfunction-associated steatohepatitis pathogenesis and liver fibrosis: From inflammation to therapeutic targets.Hepatology communications · 2025Review
- The Intriguing Roles of Cytokines in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Narrative Review.Current obesity reports · 2025Review
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Novel RORγt inverse agonists limit IL-17-mediated liver inflammation and fibrosis.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Hemopexin and HO-1 induction during acute colitis in mice is dependent on interleukin-22.Frontiers in immunology · 2025Article
- Type I IFN receptor blockade alleviates liver fibrosis through macrophage-derived STAT3 signaling.Frontiers in immunology · 2025Article
- IL-22-STAT3-CD155 axis in alveolar echinococcosis: a pivotal role in immune exhaustion and therapeutic potential.Frontiers in immunology · 2025Article
- Pancreatic beta-cell IL-22 receptor deficiency induces age-dependent dysregulation of insulin biosynthesis and systemic glucose homeostasis.Nature communications · 2024Article
- Role of the type 3 cytokines IL-17 and IL-22 in modulating metabolic dysfunction-associated steatotic liver disease.Frontiers in immunology · 2024Review
- Review
- Multifunctional roles of inflammation and its causative factors in primary liver cancer: A literature review.World journal of hepatology · 2023Review
- Review
- Liver Injury and Regeneration: Current Understanding, New Approaches, and Future Perspectives.Cells · 2023Review
- The Effect of Sex-Specific Differences on IL-10International journal of molecular sciences · 2023Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsNonalcoholic fatty liver disease (NAFLD) is a major health problem with complex pathogenesis. Although sex differences in NAFLD pathogenesis have been reported, the mechanisms underlying such differences remain understudied. Interleukin (IL)22 is a pleiotropic cytokine with both protective and/or pathogenic effects during liver injury. IL22 was shown to be hepatoprotective in NAFLD-related liver injury. However, these studies relied primarily on exogenous administration of IL22 and did not examine the sex-dependent effect of IL22. Here, we sought to characterize the role of endogenous IL22-receptor signaling during NAFLD-induced liver injury in males and females.
methodsWe used immunofluorescence, flow cytometry, histopathologic assessment, and gene expression analysis to examine IL22 production and characterize the intrahepatic immune landscape in human subjects with NAFLD (n = 20; 11 men and 9 women) and in an in vivo Western high-fat diet-induced NAFLD model in IL22RA knock out mice and their wild-type littermates.
resultsExamination of publicly available data sets from 2 cohorts with NAFLD showed increased hepatic IL22 gene expression in females compared with males. Furthermore, our immunofluorescence analysis of liver sections from NAFLD subjects (n = 20) showed increased infiltration of IL22-producing cells in females. Similarly, IL22-producing cells were increased in wild-type female mice with NAFLD and the hepatic IL22/IL22 binding protein messenger RNA ratio correlated with expression of anti-apoptosis genes. The lack of endogenous IL22-receptor signaling (IL22RA knockout) led to exacerbated liver damage, inflammation, apoptosis, and liver fibrosis in female, but not male, mice with NAFLD.
conclusionsOur data suggest a sex-dependent hepatoprotective antiapoptotic effect of IL22-receptor signaling during NAFLD-related liver injury in females.
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Registered trials
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.