دورية أكاديمية
Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells.
| العنوان: | Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells. |
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| المؤلفون: | Tay RE; Department of Immunology, Harvard Medical School, Boston, MA.; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA., Olawoyin O; Department of Immunology, Harvard Medical School, Boston, MA.; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA., Cejas P; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA., Xie Y; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA., Meyer CA; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA., Ito Y, Weng QY; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA., Fisher DE; Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA., Long HW; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA., Brown M; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Kim HJ; Department of Immunology, Harvard Medical School, Boston, MA.; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA., Wucherpfennig KW; Department of Immunology, Harvard Medical School, Boston, MA.; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA. |
| المصدر: | The Journal of experimental medicine [J Exp Med] 2020 Jul 06; Vol. 217 (7). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Rockefeller University Press |
| مواضيع طبية MeSH: | Epigenesis, Genetic*/drug effects , T-Lymphocytes, Cytotoxic*/drug effects, CD8-Positive T-Lymphocytes/*immunology , Histone Deacetylases/*metabolism, Acetylation/drug effects ; Acrylamides/pharmacology ; Animals ; Antigens/metabolism ; Base Sequence ; CD8-Positive T-Lymphocytes/drug effects ; Core Binding Factor Alpha 3 Subunit/metabolism ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylases/deficiency ; Histones/metabolism ; Lymph Nodes/drug effects ; Lymph Nodes/metabolism ; Lymphocyte Activation/drug effects ; Lymphocyte Activation/immunology ; Lymphocytic choriomeningitis virus/physiology ; Lysine/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; Phenylenediamines/pharmacology ; Positive Regulatory Domain I-Binding Factor 1/metabolism ; Transcription, Genetic/drug effects |
| مستخلص: | Cytotoxic T cells play a key role in adaptive immunity by killing infected or cancerous cells. While the transcriptional control of CD8 T cell differentiation and effector function following T cell activation has been extensively studied, little is known about epigenetic regulation of these processes. Here we show that the histone deacetylase HDAC3 inhibits CD8 T cell cytotoxicity early during activation and is required for persistence of activated CD8 T cells following resolution of an acute infection. Mechanistically, HDAC3 inhibits gene programs associated with cytotoxicity and effector differentiation of CD8 T cells including genes encoding essential cytotoxicity proteins and key transcription factors. These data identify HDAC3 as an epigenetic regulator of the CD8 T cell cytotoxicity program. Competing Interests: Disclosures: Dr. Fisher reported a financial interest in Soltego, Inc., a company developing SIK inhibitors for topical skin darkening treatments that might be used for a broad set of human applications. Dr. Fisher's interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. Dr. Brown reported grants from Novartis and personal fees from H3 Biomedicine, Kronos Bio, Aleta Biotherapeutics, and GV20 Therapeutics outside the submitted work. Dr. Wucherpfennig reported grants from Novartis during the conduct of the study; personal fees from TCR2 Therapeutics, T-Scan Therapeutics, Immunitas Therapeutics, and Nextechinvest outside the submitted work. No other disclosures were reported. (© 2020 Tay et al.) |
| التعليقات: | Erratum in: J Exp Med. 2020 Jul 6;217(7):. (PMID: 32441763) |
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| معلومات مُعتمدة: | R01 AR072304 United States AR NIAMS NIH HHS; R01 CA238039 United States CA NCI NIH HHS; P01 CA163222 United States CA NCI NIH HHS; R01 CA222871 United States CA NCI NIH HHS; R01 AR043369 United States AR NIAMS NIH HHS |
| المشرفين على المادة: | 0 (Acrylamides) 0 (Antigens) 0 (Core Binding Factor Alpha 3 Subunit) 0 (Histone Deacetylase Inhibitors) 0 (Histones) 0 (Phenylenediamines) 0 (Prdm1 protein, mouse) 0 (RGFP966) EC 2.1.1.- (Positive Regulatory Domain I-Binding Factor 1) EC 3.5.1.98 (Histone Deacetylases) EC 3.5.1.98 (histone deacetylase 3) K3Z4F929H6 (Lysine) |
| تواريخ الأحداث: | Date Created: 20200507 Date Completed: 20210216 Latest Revision: 20210216 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7336313 |
| DOI: | 10.1084/jem.20191453 |
| PMID: | 32374402 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1540-9538 |
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| DOI: | 10.1084/jem.20191453 |