Foxp3-dependent and -independent functions of peripherally-induced Treg cells [08075]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA735531 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14744463_1.fastq.gz | Fastqsanger.gz | |||
| SRR14744463_2.fastq.gz | Fastqsanger.gz | |||
| SRR14744464_1.fastq.gz | Fastqsanger.gz | |||
| SRR14744464_2.fastq.gz | Fastqsanger.gz | |||
| SRR14744465_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Foxp3-dependent and -independent functions of peripherally-induced Treg cells
| PRJNA735530 | ENA
Project description:Foxp3-dependent and -independent functions of peripherally-induced Treg cells [09748]
| PRJNA735532 | ENA
Project description:Regulatory T (Treg) cells expressing the lineage-defining transcription factor Foxp3 are essential for the maintenance of immune tolerance. Foxp3 expression can be induced in a subset of developing self-reactive thymocytes to yield thymic Treg (tTreg) cells, critical for tolerance against self-antigens. Alternatively, activation of mature naïve T cells under non-inflammatory conditions can drive the differentiation of peripherally-induced Treg (pTreg) cells, thought to contribute to tolerance against commensal microbes and dietary antigens. While Foxp3 is indispensable for tTreg cell development and function, its role in pTreg cells has remained unknown. Here, we used a genetic fate mapping approach to characterize polyclonal pTreg cells induced by microbial colonization. We found that expression of a pTreg cell-specific gene expression program was initiated in the mesenteric lymph node (mLN) in a Foxp3-independent manner. Moreover, in contrast to Treg cells in secondary lymphoid tissues, colonic microbiota-dependent pTreg cells did not depend on Foxp3 for their fitness or lineage commitment and were capable of suppressing colonic effector T cell expansion in a Foxp3-independent manner. Rather, Foxp3 was required in a cell-intrinsic manner to limit IL-17 production and to prevent the expansion of intestinal mast cells. Our results suggest that, extrathymic Foxp3 induction likely acts as a mechanism to fine-tune the activity of Th17-like cells with Foxp3-independent regulatory functions.
2021-12-31 | GSE176235 | GEO
Project description:Regulatory T (Treg) cells expressing the lineage-defining transcription factor Foxp3 are essential for the maintenance of immune tolerance. Foxp3 expression can be induced in a subset of developing self-reactive thymocytes to yield thymic Treg (tTreg) cells, critical for tolerance against self-antigens. Alternatively, activation of mature naïve T cells under non-inflammatory conditions can drive the differentiation of peripherally-induced Treg (pTreg) cells, thought to contribute to tolerance against commensal microbes and dietary antigens. While Foxp3 is indispensable for tTreg cell development and function, its role in pTreg cells has remained unknown. Here, we used a genetic fate mapping approach to characterize polyclonal pTreg cells induced by microbial colonization. We found that expression of a pTreg cell-specific gene expression program was initiated in the mesenteric lymph node (mLN) in a Foxp3-independent manner. Moreover, in contrast to Treg cells in secondary lymphoid tissues, colonic microbiota-dependent pTreg cells did not depend on Foxp3 for their fitness or lineage commitment and were capable of suppressing colonic effector T cell expansion in a Foxp3-independent manner. Rather, Foxp3 was required in a cell-intrinsic manner to limit IL-17 production and to prevent the expansion of intestinal mast cells. Our results suggest that, extrathymic Foxp3 induction likely acts as a mechanism to fine-tune the activity of Th17-like cells with Foxp3-independent regulatory functions.
2021-12-31 | GSE176236 | GEO
Project description:Regulatory T (Treg) cells expressing the X-linked lineage-defining transcription factor (TF) Foxp3 are essential for preventing fatal autoimmunity. During thymic differentiation, Foxp3 expression is induced in a subset of developing self-reactive thymocytes yielding thymic Treg (tTreg) cells, critical for enforcing tolerance to “self”. In the periphery, Foxp3 induction in mature naïve CD4 T cells activated under particular conditions results in extrathymic generation of Treg (pTreg) cells, thought to contribute to tolerance against commensal microbiota and dietary antigens. While Foxp3 is indispensable for tTreg cell differentiation and function, its role in pTreg cells has remained unknown. Here, we used complementary genetic approaches to characterize pTreg cells induced by microbial colonization and elucidate a role for Foxp3 in these cells. We found that a pTreg cell-specific gene expression program was installed in the gut-draining mesenteric lymph nodes (mLN) in a Foxp3-independent manner. In contrast to tTreg cells residing in the secondary lymphoid tissues, colonic microbiota-dependent pTreg cells did not depend on Foxp3 for their fitness or lineage commitment and were capable of preventing colonic effector T cell expansion in a Foxp3-independent manner. Rather, Foxp3 acted in a cell intrinsic manner to limit IL-17 production and was critical for the suppression of rampant intestinal mastocytosis. Thus, in contrast to tTreg cells, whose functionality is entirely Foxp3-dependent, Foxp3 expression plays a notably nuanced role in pTreg cells and acts to fine-tune the activity of IL-17 producing cells with Foxp3-independent regulatory functions.
2022-06-17 | GSE176293 | GEO
Project description:Foxp3-dependent and -independent functions of peripherally-induced regulatory T cells: scRNA-seq
| PRJNA735737 | ENA
Project description:Regulatory T (Treg) cells expressing the transcription factor Foxp3 are an essential suppressive CD4 T cell lineage of dual origin: Foxp3 induction in thymocytes and mature CD4 T cells gives rise to thymic (tTreg) and peripheral (pTreg) Treg cells, respectively. While tTreg cells primarily suppress autoimmunity, pTreg cells are thought to enforce tolerance to food and commensal microbiota. However, the role of Foxp3 in pTreg cells and the mechanisms underlying their differentiation and function remain poorly understood. Here, we used genetic lineage tracing to unambiguously identify microbiota-induced pTreg cells and found that many of their distinct features were Foxp3-independent. Lineage-committed, microbiota-dependent pTreg-like cells persisted in the colon in the absence of Foxp3 protein. While Foxp3 was critical for the suppression of a Th17 cell program, colitis and rampant mastocytosis, pTreg cells suppressed colonic effector T cell expansion in a Foxp3-independent manner. Thus, Foxp3 and the tolerogenic signals that precede and promote its expression independently confer distinct facets of pTreg functionality.
2022-06-17 | GSE193780 | GEO
Project description:Foxp3 Dependent and Independent Functions of Peripherally Induced Regulatory T Cells: colonic scRNA+TCR-seq
| PRJNA797854 | ENA
Project description:Regulatory T cells (Treg) have been shown to adopt a catabolic metabolic programme with increased capacity for fatty acid oxidation fuelled oxidative phosphorylation (OXPHOS). The role of Foxp3 in this metabolic shift is poorly understood. Here we show that Foxp3 was sufficient to induce a significant increase in the spare respiratory capacity of the cell, the extra OXPHOS capacity available to a cell to meet increased demands on energy in response to work. Foxp3-expressing cells were enhanced in their ability to utilise palmitate for respiration and, in addition, the activity of electron transport complexes I, II and IV were enhanced following Foxp3 expression. Foxp3 also imparts a selective advantage in ATP generation capacity, one that might be exploited as a source of adenosine for functional immunomodulation. In order to explore possible mechanisms for these differences in metabolism we conducted a quantitative proteomics study to compare the contribution of TGFβ and the transcription factor Foxp3 to the Treg proteome. We used quantitative mass spectrometry to examine differences between proteomes of nuclear and cytoplasmic Foxp3-containing CD4+ T cells from various sources with Foxp3- activated CD4 T cells, as well as Treg from human peripheral blood. Gene set enrichment analysis of our proteomic datasets demonstrated that Foxp3 expression is associated with a significant up regulation of several members of the mitochondrial electron transport chain. Not only does Foxp3 influence genes directly concerned with immune function, but also with the energy generating functions of Treg.
2017-02-15 | PXD001906 | Pride
Project description:Natural CD4+FOXP3+ regulatory T (Treg) cells constitute a unique T-cell lineage that plays a pivotal role in maintaining immune homeostasis and immune tolerance. Recent studies provide evidence for the heterogeneity and plasticity of the Treg cell lineage. However, the fate of human Treg cells after loss of FOXP3 expression and the underlying epigenetic mechanisms remain to be fully elucidated. Here, we compared gene expression profiles and histone methylation status on two histone H3 lysine residues (H3K4me3 and H3K27me3) of expanded FOXP3+ and corresponding FOXP3-losing Treg cells. DGE assay showed that human Treg cells down-regulated Treg signature genes, whereas up-regulated a set of Th lineages-associated genes, especially for Th2, such as GATA3, GFI1 and IL13, after in vitro expansion. Furthermore, we found that reprogramming of Treg cells was associated with histone modifications, as shown by decreased abundance of permissive H3K4me3 within down-regulated Treg signature genes, such as FOXP3, CTLA4 and LRRC32 loci, although with no significant changes in H3K27me3 modification. Thus, our results indicate that human Treg cells could convert into a Th-like cells upon in vitro expansion, displaying a gene expression signature dominated by Th2 lineage associated genes, and the histone methylation might contribute to such conversion. mRNA profiles of in-vitro-expanded FOXP3+ Treg and FOXP3-losing Treg cells generated by deep sequencing.
2013-06-06 | E-GEOD-47636 | biostudies-arrayexpress