ArticleJournal of hepatology2021
Altered aryl-hydrocarbon-receptor signalling affects regulatory and effector cell immunity in autoimmune hepatitis.
Article in Journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- High-dimensional analysis of the adenosine pathway in high-grade serous ovarian cancer.Journal for immunotherapy of cancer · 2021Pooled it
- Environmental shaping of tolerance failure in autoimmune liver diseases: a phenotype-specific framework with primary biliary cholangitis as the strongest model.Journal of translational autoimmunity · 2026Review
- Immunomodulatory effects of tacrolimus-loaded lipid-core nanocapsules in autoimmune hepatitis.Journal of autoimmunity · 2026Article
- Article
- Review
- Autoimmune Hepatitis: A Review of Molecular Mechanisms and Research Gaps in African Populations.Biology · 2026Review
- Regulatory T-cells in autoimmune hepatitis: An historical perspective with hints to the future.JHEP reports : innovation in hepatology · 2026Article
- Inhibition of estrogen receptor alpha stabilizes regulatory T cell function in autoimmune hepatitis.JHEP reports : innovation in hepatology · 2026Article
- An imbalance between CD80 and CD86 levels and CD4 regulatory T cell number and transendocytosis function exists in the liver in autoimmune hepatitis.Clinical and experimental immunology · 2026Article
- Gut microbiota in Henoch-Schönlein purpura: from pathogenesis to therapeutic strategies.Frontiers in immunology · 2026Review
- Hepatic Arachidonic Acid Dysregulation Impairs Double-Negative Regulatory T Cell-Mediated Immunoregulation via CD39 Downregulation and Drives MASLD Development.Journal of immunology research · 2026Article
- Neutrophil-T cell cross talk in noninfectious liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2026Review
- Gut microbial metabolites of amino acids in liver diseases.Gut microbes · 2025Review
- Tryptophan catabolites from microbiota ameliorate immune-mediated hepatitis through activating aryl hydrocarbon receptor of T cells.Gut microbes · 2025Article
- Antisense to human CD39 dysregulates immune metabolism in inflammatory bowel disease.Cellular & molecular immunology · 2025Article
- Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications.MedComm · 2025Review
- Clinical management of autoimmune liver diseases: juncture, opportunities, and challenges ahead.Immunologic research · 2025Review
- Purinergic signaling by TCRαβScience bulletin · 2025Article
- Aryl hydrocarbon receptor-regulated long non-coding RNAs: implications for glycolipid metabolism and prognosis in hepatocellular carcinoma.Frontiers in oncology · 2025Article
- Interacting roles of gut microbiota and T cells in the development of autoimmune hepatitis.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsIn autoimmune hepatitis (AIH), the imbalance between regulatory T cells (Tregs) and T-helper type 17 (Th17) cells has been linked to low levels of CD39, an ectoenzyme that hydrolyses ATP, ultimately generating immunosuppressive adenosine. Upregulation of CD39 results from activation of aryl hydrocarbon receptor (AHR), which mediates toxin responses to modulate T-cell immunity. In this study, we investigated whether altered AHR signalling underlies defective CD39 expression and function in AIH Tregs and Th17 cells, therefore contributing to regulatory/effector cell imbalance.
methodsTregs and Th17 cells, obtained from the peripheral blood of 49 patients with AIH and 21 healthy individuals (HI), were tested for response to endogenous and exogenous AHR ligands.
resultsWhen compared to those of HI, AIH-derived Tregs and Th17 cells displayed impaired responses to AHR activation, reflected by impaired upregulation of CD39, delayed increase in ectoenzymatic activity, and defective Treg suppressive function. These impairments resulted, at least in part, from heightened levels of AHRR and Erα in Tregs and high HIF-1α in Th17 cells, and were reverted upon molecular blockade. Importantly, in AIH-derived Tregs, the binding affinity of AHR was higher for Erα than ARNT.
conclusionsIn AIH, high levels of AHRR and HIF-1α inhibit AHR signalling in Tregs and Th17 cells. AHR non-canonical binding to Erα further amplifies the lack of effective CD39 upregulation. Blockade of these inhibitory and/or non-canonical activation pathways represents a potential therapeutic approach to restore CD39 and immunohomeostasis in AIH. LAY SUMMARY: In patients with autoimmune hepatitis, the imbalance between regulatory T cells and T helper type-17 cells is linked to dysfunction of the aryl hydrocarbon receptor pathway, resulting from aberrant inhibition or non-canonical activation. These alterations impair Treg- and Th17 cell-induced upregulation of CD39, an ectoenzyme key to immunoregulation. Blockade of excessive inhibition or non-canonical activation of the aryl hydrocarbon receptor pathway might represent a novel therapeutic strategy to control inflammation while restoring immune balance in autoimmune hepatitis.
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