دورية أكاديمية
Single-cell RNA-seq reveals TOX as a key regulator of CD8 + T cell persistence in chronic infection.
| العنوان: | Single-cell RNA-seq reveals TOX as a key regulator of CD8 + T cell persistence in chronic infection. |
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| المؤلفون: | Yao C; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA., Sun HW; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA., Lacey NE; National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Ji Y; National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.; Cellular Biomedicine Group, Gaithersburg, MD, USA., Moseman EA; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.; Department of Immunology, Duke University School of Medicine, Durham, NC, USA., Shih HY; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA., Heuston EF; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Kirby M; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Anderson S; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Cheng J; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Khan O; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School Medicine, Philadelphia, PA, USA., Handon R; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Reilley J; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Fioravanti J; National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Hu J; National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Gossa S; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA., Wherry EJ; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School Medicine, Philadelphia, PA, USA., Gattinoni L; National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., McGavern DB; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA., O'Shea JJ; National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA. osheaj@arb.niams.nih.gov., Schwartzberg PL; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. pams@nih.gov.; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. pams@nih.gov., Wu T; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. tuoqi.wu@ucdenver.edu.; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. tuoqi.wu@ucdenver.edu.; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA. tuoqi.wu@ucdenver.edu. |
| المصدر: | Nature immunology [Nat Immunol] 2019 Jul; Vol. 20 (7), pp. 890-901. Date of Electronic Publication: 2019 Jun 17. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2916 (Electronic) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Nature America Inc. c2000- |
| مواضيع طبية MeSH: | Gene Expression Regulation* , Single-Cell Analysis*, CD8-Positive T-Lymphocytes/*immunology , CD8-Positive T-Lymphocytes/*metabolism , Homeodomain Proteins/*genetics , Infections/*etiology, Animals ; Biomarkers ; Chromatin Immunoprecipitation ; Epigenesis, Genetic ; Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; Homeodomain Proteins/metabolism ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Immunologic Memory ; Infections/metabolism ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic Choriomeningitis/virology ; Lymphocytic choriomeningitis virus/immunology ; Mice ; Time Factors ; Transcriptome |
| مستخلص: | Progenitor-like CD8 + T cells mediate long-term immunity to chronic infection and cancer and respond potently to immune checkpoint blockade. These cells share transcriptional regulators with memory precursor cells, including T cell-specific transcription factor 1 (TCF1), but it is unclear whether they adopt distinct programs to adapt to the immunosuppressive environment. By comparing the single-cell transcriptomes and epigenetic profiles of CD8 + T cells responding to acute and chronic viral infections, we found that progenitor-like CD8 + T cells became distinct from memory precursor cells before the peak of the T cell response. We discovered a coexpression gene module containing Tox that exhibited higher transcriptional activity associated with more abundant active histone marks in progenitor-like cells than memory precursor cells. Moreover, thymocyte selection-associated high mobility group box protein TOX (TOX) promoted the persistence of antiviral CD8 + T cells and was required for the programming of progenitor-like CD8 + T cells. Thus, long-term CD8 + T cell immunity to chronic viral infection requires unique transcriptional and epigenetic programs associated with the transcription factor TOX. |
| التعليقات: | Comment in: Cell Mol Immunol. 2020 May;17(5):558-560. (PMID: 31515505) |
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| معلومات مُعتمدة: | K99 AG056524 United States AG NIA NIH HHS; R00 AG056524 United States AG NIA NIH HHS; Z99 AI999999 United States ImNIH Intramural NIH HHS |
| المشرفين على المادة: | 0 (Biomarkers) 0 (Homeodomain Proteins) 0 (Rhox8 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20190619 Date Completed: 20190709 Latest Revision: 20220420 |
| رمز التحديث: | 20240513 |
| مُعرف محوري في PubMed: | PMC6588409 |
| DOI: | 10.1038/s41590-019-0403-4 |
| PMID: | 31209400 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1529-2916 |
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| DOI: | 10.1038/s41590-019-0403-4 |