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Pre-transplant conditioning propagates selective loss of host Helios+/Nrp1+ Treg in aHSCT

ABSTRACT: Pre-transplant conditioning propagates selective loss of host Helios+/Nrp1+ Treg in aHSCT

PROVIDER: PRJNA947518 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23938839_1.fastq.gz	Fastqsanger.gz
	SRR23938839_2.fastq.gz	Fastqsanger.gz
	SRR23938840_1.fastq.gz	Fastqsanger.gz
	SRR23938840_2.fastq.gz	Fastqsanger.gz
	SRR23938841_1.fastq.gz	Fastqsanger.gz

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Pre-transplant conditioning propagates selective loss of host Helios+/Nrp1+ Treg in aHSCT

Project description:Comparative analysis of four murine Treg subsets differentially affected by pre-transplant conditioning and acute gastrointestinal GvHD following allogeneic hematopoietic stem cell transplantation.

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Comparison of Splenic Nrp1- and Nrp1+ Treg Populations

Project description:To compare subpopulations of Treg cells in wild type mice based upon Nrp1 Expression, differentiating nTreg and iTreg Cells were FACS sorted based upon expression of CD4, Foxp3 and expression of Nrp1.

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Comparison of Splenic Nrp1- and Nrp1+ Treg Populations

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Helios expression defines two distinct populations of Foxp3+ Treg cells

Project description:The transcription factor Helios is expressed in a large subset of Foxp3+ Tregs of both mouse and man. We previously demonstrated that Treg induced in peripheral sites (pTreg) from Foxp3- T conventional (Tconv) cells were Helios- and proposed that Helios is a marker of thymic derived Treg (tTreg). To compare the two Treg subpopulations, we generated Helios-GFP reporter mice and crossed them to Foxp3-RFP reporter mice. The Helios+ Treg population expressed a more activated phenotype and had a higher suppressive capacity in vitro. Both populations expressed a highly demethylated TSDR and both subsets were equivalent in their ability to suppress inflammatory bowel disease in vivo. However, Helios+ Treg more effectively inhibited the proliferation of activated, autoreactive splenocytes from scurfy mice. When Helios+ and Helios- Treg were transferred to lymphoreplete mice, both populations maintained comparable Foxp3 expression, but Foxp3 expression was less stable in Helios- Treg when transferred to lymphopenic mice. Gene expression profiling of the two populations demonstrated a large number of differentially expressed genes and that Helios- Treg subpopulation expressed certain genes normally expressed in CD4+Foxp3- T cells. TCR repertoire analysis indicated very little overlap between Helios+ and Helios- Treg. Thus, Helios+ and Helios- Treg subpopulations are phenotypically and functionally distinct, consistent with thymic and peripheral sites of origin, respectively. Because of their superior suppressive activity and enhanced stability Foxp3+Helios+ Treg represent the optimal Treg population for cellular immunotherapy.

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Wildtype and NRP1 knockout macrophages

Project description:Obesity gives rise to metabolic complications by mechanisms that are poorly understood. While chronic inflammatory signaling in adipose tissue is typically associated with metabolic deficiencies linked to excessive weight gain, we identified a subset of NRP1-expressing myeloid cells that accumulate in adipose tissue and protect against obesity and metabolic syndrome. Ablation of NRP1 in macrophages compromised lipid uptake in these cells, which reduced substrates for fatty acid β-oxidation and shifted energy metabolism of these macrophages towards a more inflammatory glycolytic metabolism. Conditional deletion of NRP1 in LysM Cre-expressing cells lead to inadequate adipose vascularization, accelerated weight gain and reduced insulin sensitivity even independent of weight gain. Transfer of NRP1+ hematopoietic cells improved glucose homeostasis, resulting in the reversal of a prediabetic phenotype. Our findings suggest a pivotal role for adipose tissue resident NRP1+-expressing macrophages in driving healthy weight gain and maintaining glucose tolerance.

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Helios KO Tregs

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Conditioning-1

Project description:Conditioning-1

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ChIP-seq HELIOS (Ikzf2)

Project description:Here we addressed the genome-wide DNA binding profile of Helios transcription factor in early hematopoietic progenitor cells. We reported Helios DNA target sites by performing Chromatin Immuno-Precipitation (ChIP) assay on genomic DNA from the early hematopoietic progenitor cells line HPC7.

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Influence of ATL-type Helios overexpression or WT-Helios/Ikaros knockdown on gene expression profile in Jurkat cells

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