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Gene regulatory basis of bystander activation in CD8+ T cells (ATAC-seq)

ABSTRACT: Gene regulatory basis of bystander activation in CD8+ T cells (ATAC-seq)

PROVIDER: PRJNA749294 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15228844_1.fastq.gz	Fastqsanger.gz
	SRR15228844_2.fastq.gz	Fastqsanger.gz
	SRR15228845_1.fastq.gz	Fastqsanger.gz
	SRR15228845_2.fastq.gz	Fastqsanger.gz
	SRR15228846_1.fastq.gz	Fastqsanger.gz

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Gene regulatory basis of bystander activation in CD8+ T cells

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After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism

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Gene regulatory basis of bystander activation in CD8+ T cells (ATAC-seq)

Project description:The immune system is stratified into layers of specialized cells with distinct functions. Recently, Lin28b was shown to serve as a master regulator of fetal lymphopoiesis and program the development of more innate-like lymphocytes in early life. However, it is still unclear how Lin28b alters the function of fetal-derived lymphocytes and protects the host against infection. In this report, we examined how Lin28b transcriptionally and epigenetically programs murine CD8+ T cells for innate immune defense and translated our key findings to human CD8+ T cells. We found that Lin28b operates as a gatekeeper, opening the door to a hidden diversity of phenotypes that are unveiled upon stimulation with innate cytokines. In particular, Lin28b promotes a transcriptionally and functionally diverse pool of cells through chromatin remodeling. As a result, neonatal CD8+ T cells are able to deploy a bet-hedging immune strategy and protect the host against a wide range of unrelated pathogens.

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Project description:CD8+ T cells have been categorized as an adaptive lymphocyte, based on their ability to recognize specific foreign antigens and mount memory responses. However, neonatal and adult CD8+ T cells are derived from distinct HSC progenitors, which may alter the roles they play during infection. Here, we demonstrate that neonatal CD8+ T cells can be activated by innate cytokines alone and protect the host from a variety of unrelated pathogens in the absence of TCR signaling. Using a multi-omics approach, we found that neonatal CD8+ T cells are highly responsive to innate cytokines because they can rapidly undergo chromatin remodeling, resulting in the usage of a distinct set of enhancers that are more commonly found in innate-like T cells. We also identified a key gene regulatory axis (Bach2/AP1) that is differentially utilized by neonatal and adult CD8+ T cells to toggle their responsiveness to innate cytokines. Importantly, the developmental switch between innate and adaptive functions in the CD8+ T cell compartment is not mediated by a change in the maturation of individual cells along a linear axis, but rather by changes in the abundance of distinct subsets of cells. Collectively, our findings provide support for the layered immune hypothesis and indicate that the CD8+ T cell compartment is more phenotypically diverse than previously thought.

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