ArticleThe Journal of clinical investigation2018
SUMO-defective c-Maf preferentially transactivates Il21 to exacerbate autoimmune diabetes.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- ROS-SUMO Crosstalk in Oxidative Stress: Disease Mechanisms and Reproductive Health.Antioxidants (Basel, Switzerland) · 2026Review
- Immune regulation by the SUMO family.Nature reviews. Immunology · 2025Review
- Ubiquitin-like Proteins in Autoimmune Diseases: Current Evidence and Therapeutic Opportunities.Immune network · 2025Review
- Transcription factor c-Maf: a checkpoint that programs autoimmunity.Frontiers in immunology · 2025Review
- A p-n heterojunction sonosensitizer for improved sono-immunotherapy via induction of multimodal cell death mechanisms.Theranostics · 2025Article
- Regulation of the immune microenvironment by SUMO in diabetes mellitus.Frontiers in immunology · 2025Review
- Mechanisms and functions of SUMOylation in health and disease: a review focusing on immune cells.Journal of biomedical science · 2024Review
- Heterogeneity of Islet-Infiltrating IL-21+ CD4 T Cells in a Mouse Model of Type 1 Diabetes.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Posttranslational modifications in diabetes: Mechanisms and functions.Reviews in endocrine & metabolic disorders · 2022Review
- Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling.Immunity · 2022Article
- Blimp-1 molds the epigenetic architecture of IL-21-mediated autoimmune diseases through an autoregulatory circuit.JCI insight · 2022Article
- Molecular Mechanisms Driving IL-10- Producing B Cells Functions: STAT3 and c-MAF as Underestimated Central Key Regulators?Frontiers in immunology · 2022Article
- An update on epigenetic regulation in autoimmune diseases.Journal of translational autoimmunity · 2022Article
- Post-Translational Modifications in Transcription Factors that Determine T Helper Cell Differentiation.Molecules and cells · 2021Review
- SUMO and SUMOylation Pathway at the Forefront of Host Immune Response.Frontiers in cell and developmental biology · 2021Review
- Post-Translational Modifications of Transcription Factors Harnessing the Etiology and Pathophysiology in Colonic Diseases.International journal of molecular sciences · 2020Review
- c-MAF, a Swiss Army Knife for Tolerance in Lymphocytes.Frontiers in immunology · 2020Review
- Loss of ubiquitin-conjugating enzyme E2 (Ubc9) in macrophages exacerbates multiple low-dose streptozotocin-induced diabetes by attenuating M2 macrophage polarization.Cell death & disease · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SUMOylation is involved in the development of several inflammatory diseases, but the physiological significance of SUMO-modulated c-Maf in autoimmune diabetes is not completely understood. Here, we report that an age-dependent attenuation of c-Maf SUMOylation in CD4+ T cells is positively correlated with the IL-21-mediated diabetogenesis in NOD mice. Using 2 strains of T cell-specific transgenic NOD mice overexpressing wild-type c-Maf (Tg-WTc) or SUMOylation site-mutated c-Maf (Tg-KRc), we demonstrated that Tg-KRc mice developed diabetes more rapidly than Tg-WTc mice in a CD4+ T cell-autonomous manner. Moreover, SUMO-defective c-Maf preferentially transactivated Il21 to promote the development of CD4+ T cells with an extrafollicular helper T cell phenotype and expand the numbers of granzyme B-producing effector/memory CD8+ T cells. Furthermore, SUMO-defective c-Maf selectively inhibited recruitment of Daxx/HDAC2 to the Il21 promoter and enhanced histone acetylation mediated by CREB-binding protein (CBP) and p300. Using pharmacological interference with CBP/p300, we illustrated that CBP30 treatment ameliorated c-Maf-mediated/IL-21-based diabetogenesis. Taken together, our results show that the SUMOylation status of c-Maf has a stronger regulatory effect on IL-21 than the level of c-Maf expression, through an epigenetic mechanism. These findings provide new insights into how SUMOylation modulates the pathogenesis of autoimmune diabetes in a T cell-restricted manner and on the basis of a single transcription factor.
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