ArticleThe Journal of experimental medicine2021
Lack of NFATc1 SUMOylation prevents autoimmunity and alloreactivity.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Targeting NFATc1-regulated MTHFD2 one-carbon metabolism to suppress sustained T-cell-mediated inflammation in rheumatoid arthritis.Signal transduction and targeted therapy · 2026Article
- SUMOylation is destined for regulatory T cell-related immune dysregulation.Cell death discovery · 2026Review
- Non-redundant functions of NFATc1 in survival and NFATc2 in generation of exhausted CD8Frontiers in immunology · 2026Article
- The Small Ubiquitin-Like Modifier SUMO-3 Acts as a Neutrophil Chemoattractant via the Chemokine Receptors CXCR1 and CXCR2.Journal of innate immunity · 2026Article
- Immune regulation by the SUMO family.Nature reviews. Immunology · 2025Review
- BLIMP1 negatively regulates IL-2 signaling in T cells.Science advances · 2025Article
- Ubiquitin-like Proteins in Autoimmune Diseases: Current Evidence and Therapeutic Opportunities.Immune network · 2025Review
- Cellular therapies for the prevention and treatment of acute graft-versus-host disease.Stem cells (Dayton, Ohio) · 2025Review
- Article
- Inhibition of SUMOylation Induces Adaptive Antitumor Immunity against Pancreatic Cancer through Multiple Effects on the Tumor Microenvironment.Molecular cancer therapeutics · 2024Article
- NFAT signaling is indispensable for persistent memory responses of MCMV-specific CD8+ T cells.PLoS pathogens · 2024Article
- Mechanisms and functions of SUMOylation in health and disease: a review focusing on immune cells.Journal of biomedical science · 2024Review
- STIM-mediated calcium influx regulates maintenance and selection of germinal center B cells.The Journal of experimental medicine · 2024Article
- The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications.Experimental hematology & oncology · 2023Review
- Article
- Delayed and limited administration of the JAKinib tofacitinib mitigates chronic DSS-induced colitis.Frontiers in immunology · 2023Article
- Recycling and Reshaping-E3 Ligases and DUBs in the Initiation of T Cell Receptor-Mediated Signaling and Response.International journal of molecular sciences · 2022Review
- Isoform-Selective NFAT Inhibitor: Potential Usefulness and Development.International journal of molecular sciences · 2021Review
- SUMO and SUMOylation Pathway at the Forefront of Host Immune Response.Frontiers in cell and developmental biology · 2021Review
- Rapid and Efficient Gene Editing for Direct Transplantation of Naive Murine Cas9Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Posttranslational modification with SUMO is known to regulate the activity of transcription factors, but how SUMOylation of individual proteins might influence immunity is largely unexplored. The NFAT transcription factors play an essential role in antigen receptor-mediated gene regulation. SUMOylation of NFATc1 represses IL-2 in vitro, but its role in T cell-mediated immune responses in vivo is unclear. To this end, we generated a novel transgenic mouse in which SUMO modification of NFATc1 is prevented. Avoidance of NFATc1 SUMOylation ameliorated experimental autoimmune encephalomyelitis as well as graft-versus-host disease. Elevated IL-2 production in T cells promoted T reg expansion and suppressed autoreactive or alloreactive immune responses. Mechanistically, increased IL-2 secretion counteracted IL-17 and IFN-γ expression through STAT5 and Blimp-1 induction. Then, Blimp-1 repressed IL-2 itself, as well as the induced, proliferation-associated survival factor Bcl2A1. Collectively, these data demonstrate that prevention of NFATc1 SUMOylation fine-tunes T cell responses toward lasting tolerance. Thus, targeting NFATc1 SUMOylation presents a novel and promising strategy to treat T cell-mediated inflammatory diseases.
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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.