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On the role of glucocorticoid signaling in the differentiation of virus-specific CD8+ T cell memory

ABSTRACT: We show that signaling through the glucocorticoid receptor, NR3C1, regulates CD8+ T cell memory differentiation. An analysis of single cell RNASeq (scRNASeq) dataset of virus-specific CD8+ T cells revealed lower NR3C1 activity within the cluster exhibiting higher expression of memory CD8+ T cell associated genes. Dexamethasone exposure of antigen-stimulated CD8+ T cells increased the representation of memory precursors within the pool of activated cells both in vitro and in vivo during the acute phase of a resolving infection, thus elevating the pool of persisting memory. RNAseq and biochemical analysis performed on dexamethasone exposed CD8+ T cells revealed a modulation of intrinsic programming resulting in metabolic alteration, lower ROS accumulation and enhanced levels of Bcl2 expression that promoted transition of effectors into memory cells. The phenomenon was evident at a low dose of dexamethasone as higher doses caused mitochondrial toxicity. We, therefore, identify NR3C1 as a modulator of memory CD8+ T cell differentiation and provide a putative strategy for increasing the pool of anti-viral CD8+ T cell memory.

ORGANISM(S): Mus musculus

PROVIDER: GSE254273 | GEO | 2024/09/03

REPOSITORIES: GEO

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Rapid proliferation and differentiation impairs the development of memory CD8+ T cells in early life

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