ArticleCell metabolism2024
A Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation.
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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 37 papers, 2 of them syntheses that pooled it.
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37citing papers in PubMed, 2 pooled it
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37 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Glutathione in Skin Aging and Tissue Regeneration: A Systematic Review of Molecular Mechanisms, Redox Modulation, and Biomedical Implications.Molecules (Basel, Switzerland) · 2026Pooled it
- Pooled it
- The gut microbiota and host immunity synergistically orchestrate colonization resistance.Gut microbes · 2026Review
- Intrahepatic T cell analysis reveals Th17 and MAIT17 enrichment in primary sclerosing cholangitis.JHEP reports : innovation in hepatology · 2026Article
- The regulatory role of post-translational modifications in the pathogenesis of ulcerative colitis.Molecular biology reports · 2026Review
- Glutathione Biology in Neurodegenerative and Metabolic Diseases: Molecular Mechanisms, Pathophysiological Roles, and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- The Role of Anti-Inflammatory Nutrition in Metabolic Syndrome and Cardiometabolic Diseases.Nutrients · 2026Review
- Ferroptosis in T cells: mechanisms, biology and translational opportunities.Nature reviews. Immunology · 2026Review
- Rhoifolin Alleviates Ulcerative Colitis by Targeting NMNAT1 and Activating SIRT1-FOXO1 Signaling to Enhance ILC3s Effector Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pediococcus pentosaceus JNL0053 Mitigates DSS-induced Colitis in Mice Via the IL-22-Gut Barrier Pathway.Probiotics and antimicrobial proteins · 2026Article
- Glutamate-cysteine ligase catalytic related glutathione metabolism inhibited high mobility group box 1 release by regulating epithelium ferroptosis in asthma.Journal of thoracic disease · 2026Article
- Gut microbiota induces dysspermatogenesis via microbial-derived phenylacetylglycine in Ggt1-deficient mice.Microbiome · 2026Article
- Tissue and CD4 T cell subset dependence on the amino acid transporter SLC38A1.Cell metabolism · 2026Article
- Loss of Pum2 exacerbates colitis by disrupting macrophage-epithelial crosstalk and promoting epithelial necroptosis.Cell death discovery · 2026Article
- IL-22/IL-22R signaling attenuates mitochondrial damage in PCOS by modulating granulosa cell lipid metabolism through ETS1.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Social stress worsens colitis through β-adrenergic-driven oxidative stress in intestinal mucosal compartments.Brain, behavior, and immunity · 2026Article
- Dysregulated immunometabolism in gut inflammation.Acta biochimica et biophysica Sinica · 2026Review
- Inflammatory bowel diseases: pathological mechanisms and therapeutic perspectives.Molecular biomedicine · 2026Review
- Gut microbiota-derived metabolites and IL-22 signaling in inflammatory bowel disease: context-dependent regulation of mucosal repair and inflammation.Frontiers in immunology · 2026Review
- Carbon dots derived fromFrontiers in molecular biosciences · 2026Article
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Authors and funding
28 authors.
Lynn BonettiExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Veronika HorkovaExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Melanie GrusdatExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Joseph LongworthExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Luana GuerraExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Henry KurniawanExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Davide G FranchinaExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Leticia Soriano-BaguetExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Carole BinsfeldExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Charlène VerschuerenExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Sabine SpathInstitute of Experimental Immunology, Inflammation Research, University of Zurich, 8057 Zurich, Switzerland; Center for Fundamental Immunology, Benaroya Research Institute, Seattle, WA 98101, USA.
Anouk EwenExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Eric KoncinaMolecular Disease Mechanisms Group, Department of Life Sciences and Medicine, University of Luxembourg, Belval, Luxembourg.
Jean-Jacques GérardyNational Center of Pathology (NCP), Laboratoire National de Santé (LNS), Dudelange, Luxembourg; Luxembourg Center of Neuropathology (LCNP), 3555 Dudelange, Luxembourg.
Takumi KobayashiExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Catherine DostertExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Sophie FarinelleExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Janika HärmExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Yu-Tong FanExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg.
Ying ChenDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Isaac S HarrisWilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14642, USA.
Philipp A LangDepartment of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Vasilis VasiliouDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Ari WaismanInstitute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Elisabeth LetellierMolecular Disease Mechanisms Group, Department of Life Sciences and Medicine, University of Luxembourg, Belval, Luxembourg.
Burkhard BecherInstitute of Experimental Immunology, Inflammation Research, University of Zurich, 8057 Zurich, Switzerland.
Michel MittelbronnNational Center of Pathology (NCP), Laboratoire National de Santé (LNS), Dudelange, Luxembourg; Luxembourg Center of Neuropathology (LCNP), 3555 Dudelange, Luxembourg; Department of Life Sciences and Medicine (DLSM), University of Luxembourg, Esch-sur-Alzette, Luxembourg; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Faculty of Science, Technology and Medicine (FSTM), University of Luxembourg, Esch-sur-Alzette, Luxembourg; Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1526 Luxembourg, Luxembourg.
Dirk BrennerExperimental and Molecular Immunology, Department of Infection and Immunity (DII), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Immunology & Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7, Avenue des Hauts Fourneaux, Esch-sur-Alzette, Luxembourg; Odense Research Center for Anaphylaxis (ORCA), Department of Dermatology and Allergy Center, Odense University Hospital, University of Southern Denmark, Odense, Denmark. Electronic address: dirk.brenner@lih.lu.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intestinal tract generates significant reactive oxygen species (ROS), but the role of T cell antioxidant mechanisms in maintaining intestinal homeostasis is poorly understood. We used T cell-specific ablation of the catalytic subunit of glutamate cysteine ligase (Gclc), which impaired glutathione (GSH) production, crucially reducing IL-22 production by Th17 cells in the lamina propria, which is critical for gut protection. Under steady-state conditions, Gclc deficiency did not alter cytokine secretion; however, C. rodentium infection induced increased ROS and disrupted mitochondrial function and TFAM-driven mitochondrial gene expression, resulting in decreased cellular ATP. These changes impaired the PI3K/AKT/mTOR pathway, reducing phosphorylation of 4E-BP1 and consequently limiting IL-22 translation. The resultant low IL-22 levels led to poor bacterial clearance, severe intestinal damage, and high mortality. Our findings highlight a previously unrecognized, essential role of Th17 cell-intrinsic GSH in promoting mitochondrial function and cellular signaling for IL-22 protein synthesis, which is critical for intestinal integrity and defense against gastrointestinal infections.
Indexed as
GlutathioneInterleukin-22InterleukinsMitochondriaTh17 CellsAnimalsCitrobacter rodentiumEnterobacteriaceae InfectionsInflammationIntestinal MucosaIntestinesMiceMice, Inbred C57BLMice, KnockoutReactive Oxygen SpeciesSignal TransductionGlutathioneInterleukin-22InterleukinsReactive Oxygen SpeciesTOR Serine-Threonine KinasescolitisC. rodentiumgastrointestinal infectionGclcglutathioneIL-22intestinal barriermitochondrial functionROST cellsTh17 cells
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38986617What OpenQuestion holds
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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.