ID
45739
Beskrivning
Principal Investigator: Jorg J Goronzy, Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA MeSH: Aging,Antigens, Differentiation, T-Lymphocyte,T-Lymphocytes https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001187 The efficacy of the adaptive immune response declines dramatically with age, but the cell-intrinsic mechanisms driving the changes characteristic of immune aging in humans remain poorly understood. One hallmark of immune aging is the loss of self-renewing naive cells and the accumulation of differentiated but dysfunctional cells within the CD8 T cell compartment. Using ATAC-seq, we first inferred the transcription factor binding activities that maintain the naive and central and effector memory CD8 T cell states in young adults. Integrating our results with RNA-seq, we determined that BATF, ETS1, Eomes, and Sp1 govern transcription networks associated with specific CD8 T cell subset properties, including activation and proliferative potential. Extending our analysis to aged humans, we found that the differences between memory and naive CD8 T cells were largely preserved across age, but that naive and central memory cells from older individuals exhibited a shift toward a more differentiated pattern of chromatin openness. Additionally, aged naive cells displayed a loss in chromatin openness at gene promoters, a phenomenon that appears to be due largely to a loss in binding by NRF1, leading to a marked drop-off in the ability of the naive cell to initiate transcription of mitochondrial genes. Our findings identify BATF- and NRF1-driven gene regulation as targets for delaying CD8 T cell aging and restoring T cell function.
Länk
Nyckelord
Versioner (1)
- 02/06/23 02/06/23 - Chiara Middel
Rättsinnehavare
Jorg J Goronzy, Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA
Uppladdad den
2 giugno 2023
DOI
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Licens
Creative Commons BY 4.0
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dbGaP phs001187 Epigenomics of Human CD8 T cell Differentiation and Aging
Eligibility Criteria
- StudyEvent: SEV1
- Eligibility Criteria
- Subject ID, consent group, subject source, source subject ID, and affection status of participants involved in the "Epigenomics of Human CD8 T cell Differentiation and Aging" project.
- Subject ID, sample ID, sample source, source sample ID, and sample use variable obtained from participants involved in the "Epigenomics of Human CD8 T cell Differentiation and Aging" project.
- Sample ID, body site, analyte type, tumor status of sample, histological type, and sequencing center of participants involved in the "Epigenomics of Human CD8 T cell Differentiation and Aging" project.
Similar models
Eligibility Criteria
- StudyEvent: SEV1
- Eligibility Criteria
- Subject ID, consent group, subject source, source subject ID, and affection status of participants involved in the "Epigenomics of Human CD8 T cell Differentiation and Aging" project.
- Subject ID, sample ID, sample source, source sample ID, and sample use variable obtained from participants involved in the "Epigenomics of Human CD8 T cell Differentiation and Aging" project.
- Sample ID, body site, analyte type, tumor status of sample, histological type, and sequencing center of participants involved in the "Epigenomics of Human CD8 T cell Differentiation and Aging" project.
C0680251 (UMLS CUI [1,2])
C0001779 (UMLS CUI [1,2])
C1298908 (UMLS CUI [2,1])
C0680251 (UMLS CUI [2,2])
C1519386 (UMLS CUI [2,3])
C0079399 (UMLS CUI [2,4])
C0015031 (UMLS CUI [2,5])
C3854307 (UMLS CUI [2,6])
C0012634 (UMLS CUI [2,7])
C0010825 (UMLS CUI [2,8])