ArticleInternational journal of molecular sciences2021
Acetaminophen-Induced Liver Injury Exposes Murine IL-22 as Sex-Related Gene Product.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Aryl hydrocarbon receptor: a multifaceted environmental sensor in liver homeostasis and disease.Frontiers in medicine · 2026Review
- Activation of aryl hydrocarbon receptor signaling by indole-3-lactic acid from Bacillus velezensis DS2 reinforces gut mucosal immunity and attenuates inflammaging in aged mice.Immunity & ageing : I & A · 2025Article
- Testosterone affects female CD4+ T cells in healthy individuals and autoimmune liver diseases.JCI insight · 2025Article
- Bifidobacterium bifidum reduces oxidative stress and alters gut flora to mitigate acute liver injury caused by N-acetyl-p-aminophenol.BMC microbiology · 2025Article
- Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse.NPJ Regenerative medicine · 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
- Hepatic vagotomy blunts liver regeneration after hepatectomy by downregulating the expression of interleukin-22.World journal of gastrointestinal surgery · 2023Article
- The Effect of Sex-Specific Differences on IL-10International journal of molecular sciences · 2023Article
- The immunological mechanisms and therapeutic potential in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity.Cell & bioscience · 2022Review
- Sex-Dependent Hepatoprotective Role of IL-22 Receptor Signaling in Non-Alcoholic Fatty Liver Disease-Related Fibrosis.Cellular and molecular gastroenterology and hepatology · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Gaining detailed knowledge about sex-related immunoregulation remains a crucial prerequisite for the development of adequate disease models and therapeutic strategies enabling personalized medicine. Here, the key parameter of the production of cytokines mediating disease resolution was investigated. Among these cytokines, STAT3-activating interleukin (IL)-22 is principally associated with recovery from tissue injury. By investigating paradigmatic acetaminophen-induced liver injury, we demonstrated that IL-22 expression is enhanced in female mice. Increased female IL-22 was confirmed at a cellular level using murine splenocytes stimulated by lipopolysaccharide or αCD3/CD28 to model innate or adaptive immunoactivation. Interestingly, testosterone or dihydrotestosterone reduced IL-22 production by female but not by male splenocytes. Mechanistic studies on PMA/PHA-stimulated T-cell-lymphoma EL-4 cells verified the capability of testosterone/dihydrotestosterone to reduce IL-22 production. Moreover, we demonstrated by chromatin immunoprecipitation that testosterone impairs binding of the aryl hydrocarbon receptor to xenobiotic responsive elements within the murine IL-22 promoter. Overall, female mice undergoing acute liver injury and cultured female splenocytes upon inflammatory activation display increased IL-22. This observation is likely related to the immunosuppressive effects of androgens in males. The data presented concur with more pronounced immunological alertness demonstrable in females, which may relate to the sex-specific course of some immunological disorders.
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Registered trials
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