Nature communications, 2018-08, Vol.9 (1), p.3157-11, Article 3157
2018
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- Autor(en) / Beteiligte
- Titel
- SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation
- Ist Teil von
- Nature communications, 2018-08, Vol.9 (1), p.3157-11, Article 3157
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Regulatory T (Treg) cells are essential for maintaining immune homeostasis and tolerance, but the mechanisms regulating the stability and function of Treg cells have not been fully elucidated. Here we show SUMO-specific protease 3 (SENP3) is a pivotal regulator of Treg cells that functions by controlling the SUMOylation and nuclear localization of BACH2. Treg cell-specific deletion of Senp3 results in T cell activation, autoimmune symptoms and enhanced antitumor T cell responses. SENP3-mediated BACH2 deSUMOylation prevents the nuclear export of BACH2, thereby repressing the genes associated with CD4 T effector cell differentiation and stabilizing Treg cell-specific gene signatures. Notably, SENP3 accumulation triggered by reactive oxygen species (ROS) is involved in Treg cell-mediated tumor immunosuppression. Our results not only establish the role of SENP3 in the maintenance of Treg cell stability and function via BACH2 deSUMOylation but also clarify the function of SENP3 in the regulation of ROS-induced immune tolerance.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-018-05676-6Titel-ID: cdi_doaj_primary_oai_doaj_org_article_99392c4923a841bda11bc7886d22d63c
- Format
- –
- Schlagworte
- Active Transport, Cell Nucleus, Animals, Antineoplastic Agents - metabolism, Antitumor activity, Autoimmune diseases, Autoimmunity - immunology, Basic-Leucine Zipper Transcription Factors - metabolism, Bone Marrow Cells, CD4 antigen, CD4-Positive T-Lymphocytes, Cell activation, Cell differentiation, Cell Differentiation - immunology, Cell Line, Tumor, Cell Nucleus - immunology, Clonal deletion, Cysteine Endopeptidases, Differentiation (biology), Female, Gene Deletion, Gene Expression Profiling, Gene Expression Regulation, HEK293 Cells, Homeostasis, Homeostasis - immunology, Humans, Immune Tolerance - immunology, Immunological tolerance, Immunoregulation, Immunosuppression, Localization, Lymphocyte Activation - immunology, Lymphocytes, Lymphocytes T, Melanoma, Experimental - immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear transport, Peptide Hydrolases - genetics, Peptide Hydrolases - metabolism, Reactive Oxygen Species, Stability, SUMO protein, Sumoylation - immunology, T cell receptors, T-Lymphocytes, Regulatory - immunology, T-Lymphocytes, Regulatory - metabolism, T-Lymphocytes, Regulatory - pathology