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Single-cell RNA sequencing data (SORT-seq) of Treg cells in the human postnatal thymus

ABSTRACT: Single-cell RNA sequencing data (SORT-seq) of Treg cells in the human postnatal thymus

PROVIDER: PRJEB47946 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR6912543_1.fastq.gz	Fastqsanger.gz
	ERR6912543_2.fastq.gz	Fastqsanger.gz
	ERR6912544_1.fastq.gz	Fastqsanger.gz
	ERR6912544_2.fastq.gz	Fastqsanger.gz
	ERR6912545_1.fastq.gz	Fastqsanger.gz

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Single-cell RNA sequencing data (SORT-seq) of Treg cells in the human postnatal thymus

Project description:We have performed single-cell RNA sequencing to investigate human regulatory T cell development in the thymus. Treg cells were isolated from a postnatal thymus derived from a 7-week old infant. We examined the composition of the Treg cell compartment in the human thymus and aimed to dissect developmental pathways in Treg cell development.

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Project description:Regulatory T (Treg) cells can facilitate transplant tolerance and attenuate autoimmune- and inflammatory diseases. Therefore, it is clinically relevant to stimulate Treg cell expansion and function in vivo and to create therapeutic Treg cell products in vitro. We report that TNF receptor 2 (TNFR2) is a unique costimulus for naïve, thymus-derived (t)Treg cells from human blood that promotes their differentiation into non-lymphoid tissue (NLT)-resident effector Treg cells, without Th-like polarization. In contrast, CD28 costimulation maintains a lymphoid tissue (LT)-resident Treg cell phenotype. We base this conclusion on transcriptome and proteome analysis of TNFR2- and CD28-costimulated CD4+ Treg cells and conventional T (Tconv) cells, followed by bioinformatic comparison with published transcriptomic Treg cell signatures from NLT and LT in health and disease, including autoimmunity and cancer. These analyses illuminate that TNFR2 costimulation promotes Treg cell capacity for survival, migration, immunosuppression and tissue regeneration. Functional studies confirmed improved migratory ability of TNFR2-costimulated tTreg cells. Flow cytometry validated the presence of the TNFR2-driven Treg cell signature in effector/memory Treg cells from the human placenta as opposed to blood. Thus, TNFR2 can be exploited as driver of NLT-resident Treg cell differentiation for adoptive cell therapy or antibody-based immunomodulation in human disease.

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