ID

45739

Descripción

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.

Link

dbGaP-study=phs001187

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Versiones (1)

1. 02/06/2023 02/06/2023 - Chiara Middel

Titular de derechos de autor

Jorg J Goronzy, Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA, USA

Subido en

2 de junho de 2023

DOI

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