ArticleProceedings of the National Academy of Sciences of the United States of America2013
Metallothioneins negatively regulate IL-27-induced type 1 regulatory T-cell differentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Tetrameric STAT5 regulates the formation of immune niche cells to protect stem cell regenerative repair against mucosal inflammation.Experimental & molecular medicine · 2026Article
- IL-27: A Double-Edged Sword in Immune Regulation via JAK-STAT Orchestration.Journal of immunology research · 2026Review
- Understanding How Minerals Contribute to Optimal Immune Function.Journal of immunology research · 2023Review
- High-Efficiency Retroviral Transduction for Type 1 Regulatory T Cell Differentiation.Bio-protocol · 2022Article
- Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control.Immunity · 2022Article
- The Role of Genetic Factors in the Development of Acute Respiratory Viral Infection COVID-19: Predicting Severe Course and Outcomes.Biomedicines · 2022Article
- Differential transcriptomic changes in the central nervous system and urinary bladders of mice infected with a coronavirus.PloS one · 2022Article
- A review of possible therapies for multiple sclerosis.Molecular and cellular biochemistry · 2021Review
- Zinc Favors Triple-Negative Breast Cancer's Microenvironment Modulation and Cell Plasticity.International journal of molecular sciences · 2021Article
- Comparison of the major cell populations among osteoarthritis, Kashin-Beck disease and healthy chondrocytes by single-cell RNA-seq analysis.Cell death & disease · 2021Article
- Tr1 Cells as a Key Regulator for Maintaining Immune Homeostasis in Transplantation.Frontiers in immunology · 2021Review
- Metallothionein 1: A New Spotlight on Inflammatory Diseases.Frontiers in immunology · 2021Review
- The roles of metallothioneins in carcinogenesis.Journal of hematology & oncology · 2018Review
- Metallothioneins: Emerging Modulators in Immunity and Infection.International journal of molecular sciences · 2017Review
- Regulatory T cells in multiple sclerosis and myasthenia gravis.Journal of neuroinflammation · 2017Review
- Cancer immunotherapy by targeting immune checkpoints: mechanism of T cell dysfunction in cancer immunity and new therapeutic targets.Journal of biomedical science · 2017Review
- Metallothionein 1G promotes the differentiation of HT-29 human colorectal cancer cells.Oncology reports · 2017Article
- Metallothionein Gene Family in the Sea Urchin Paracentrotus lividus: Gene Structure, Differential Expression and Phylogenetic Analysis.International journal of molecular sciences · 2017Article
- Immunological orchestration of zinc homeostasis: The battle between host mechanisms and pathogen defenses.Archives of biochemistry and biophysics · 2016Review
- Pleiotropic roles of metallothioneins as regulators of chondrocyte apoptosis and catabolic and anabolic pathways during osteoarthritis pathogenesis.Annals of the rheumatic diseases · 2016Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
IL-27-induced type 1 regulatory T (Tr1) cells suppress autoimmunity by producing IL-10. Signal transducer and activator of transcription (STAT) 1 and STAT3 have been described as key transcription factors that promote IL-10 secretion from Tr1 cells induced by IL-27. However, the molecular pathways for negatively regulating Tr1 cell differentiation remain elusive. Here, we show that IL-27 induces metallothioneins (MTs) that in turn prevent Tr1 cell development. MT expression leads to the reduction of STAT1 and STAT3 phosphorylation under Tr1 differentiation condition, resulting in impaired IL-10 production. Accordingly, Tr1 cells derived from MT-deficient mice showed an increased ability to produce IL-10 and potently suppress experimental autoimmune encephalomyelitis upon adoptive transfer. Moreover, activation of STAT1 and/or STAT3 can overcome the suppression of IL-10 by MTs, indicating a dynamic balance between STATs and MTs in regulating IL-10 during Tr1 cell differentiation.
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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.