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Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells

ABSTRACT: Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells

PROVIDER: PRJNA731522 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14607800.fastq.gz	Fastqsanger.gz
	SRR14607801.fastq.gz	Fastqsanger.gz
	SRR14607802.fastq.gz	Fastqsanger.gz
	SRR14607803.fastq.gz	Fastqsanger.gz
	SRR14607804.fastq.gz	Fastqsanger.gz

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Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells [scRNA-seq]

Project description:Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells [scRNA-seq]

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Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells [Bulk RNA-seq]

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Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells [scRNA-seq]

Project description:CD4+ regulatory T cells (Tregs) activate and expand in response to many different types of injuries, suggesting that they play a critical role in controlling the host response to tissue damage. Here we use multi-dimensional profiling techniques to comprehensively characterize injury responsive Tregs in mice. CD44high Tregs expand in response to injury and are more suppressive than CD44low Tregs. T cell receptor (TCR) analysis reveal that CD44high Tregs undergo TCRαβ clonal expansion and increased CDR3 diversity in response to injury. Bulk and single-cell RNA sequencing with paired TCR clonotype analysis demonstrate that important Treg-associated genes were significantly differentially expressed in both CD44high and CD44low Tregs with expanded TCR clonotypes. CyTOF analysis verified protein expression of these genes on CD44high Tregs, with increases in Helios, Galectin-3 and PYCARD expression following injury. Collectively, these data provide new insights into CD44high Tregs, an important subset in the response to injury to tissue damage.

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Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells [Bulk RNA-seq]

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Multi-Dimensional Profiling Reveals a Molecularly Distinct Injury-Responsive Population of Regulatory T Cells

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Distinct Injury Responsive Regulatory T Cells Identified by Multi-Dimensional Phenotyping.

Project description:CD4+ regulatory T cells (Tregs) activate and expand in response to different types of injuries, suggesting that they play a critical role in controlling the immune response to tissue and cell damage. This project used multi-dimensional profiling techniques to comprehensively characterize injury responsive Tregs in mice. We show that CD44high Tregs expand in response to injury and were highly suppressive when compared to CD44low Tregs. T cell receptor (TCR) repertoire analysis revealed that the CD44high Treg population undergo TCRαβ clonal expansion as well as increased TCR CDR3 diversity. Bulk RNA sequencing and single-cell RNA sequencing with paired TCR clonotype analysis identified unique differences between CD44high and CD44low Tregs and specific upregulation of genes in Tregs with expanded TCR clonotypes. Gene ontology analysis for molecular function of RNA sequencing data identified chemokine receptors and cell division as the most enriched functional terms in CD44high Tregs versus CD44low Tregs. Mass cytometry (CyTOF) analysis of Tregs from injured and uninjured mice verified protein expression of these genes on CD44high Tregs, with injury-induced increases in Helios, Galectin-3 and PYCARD expression. Taken together, these data indicate that injury triggers the expansion of a highly suppressive CD44high Treg population that is transcriptionally and phenotypically distinct from CD44low Tregs suggesting that they actively participate in controlling immune responses to injury and tissue damage.

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