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Blimp1 maintains regulatory T cell identity at sites of inflammation through epigenetic imprinting

ABSTRACT: Blimp1 maintains regulatory T cell identity at sites of inflammation through epigenetic imprinting

PROVIDER: PRJNA498396 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8109570.fastq.gz	Fastqsanger.gz
	SRR8109580.fastq.gz	Fastqsanger.gz
	SRR8109571.fastq.gz	Fastqsanger.gz
	SRR8109581.fastq.gz	Fastqsanger.gz
	SRR8109572.fastq.gz	Fastqsanger.gz

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Blimp1 maintains regulatory T cell identity at sites of inflammation through epigenetic imprinting

Project description:Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. We here establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway was dependent on the transcriptional regulator Blimp1, which prevented dismantling of Foxp3 expression and "toxic" gain-of-function of Treg cells in the inflamed CNS. Blimp1 negatively regulated IL-6- and STAT3-mediated methylation of Treg cell-specific conserved non-coding sequence 2 (CNS2) in the Foxp3 locus. Consequently, CNS2 was heavily methylated when Blimp1 was ablated, leading to loss of Foxp3 expression and severe disease. These findings identify a Blimp1-dependent epigenetic pathway that preserves Treg cell stability in inflamed non-lymphoid tissues.

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Project description:Regulatory T (Treg) cells are required for peripheral tolerance. Recent evidence indicates that Treg cells can adopt specialized differentiation programs in the periphery that are controlled by transcription factors usually associated with T helper differentiation. We demonstrate that expression of the transcription factor Blimp1 defines a population of Treg cells that localize predominantly to mucosal sites and produces IL-10. Blimp1 is required for IL-10 production by these cells and for their tissue homeostasis. A list of differentially expressed genes were identified from this whole-genome expression profiling experiment. Mouse Blimp1 +/gfp and Blimp1 gfp/gfp regulatory T cells were analyzed. Three replicates each.

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