IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4+Foxp3+ regulatory T lymphocytes
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ABSTRACT:
PROVIDER: PRJNA642815 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12108277_1.fastq.gz | Fastqsanger.gz | |||
| SRR12108277_2.fastq.gz | Fastqsanger.gz | |||
| SRR12108278_1.fastq.gz | Fastqsanger.gz | |||
| SRR12108278_2.fastq.gz | Fastqsanger.gz | |||
| SRR12108279_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell precursors via the TCR, co-stimulatory receptors, and cytokine receptors. In absence of IL-2, IL-15 or their receptors, fewer Treg apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had recirculated from the periphery back to the thymus, troubling interpretation of these results. We therefore reassessed the involvement of IL-2 and IL-15 in the development of Treg, taking into account Treg-recirculation. In three-week-old mice, when substantial amounts of recirculating Treg are present in the thymus, we found similarly reduced proportions of newly developed Treg in absence of IL-2 or IL-15, and in absence of both cytokines even less Treg developed. In neonates, when practically no recirculating Treg were found in the thymus, the absence of IL-2 led to substantially more reduced Treg-development than deficiency in IL-15. IL-2 and IL-15 differentially modulated the CD25, GITR, OX40, and CD73-phenotypes of thymus-egress-competent and periphery-seeding Treg. Interestingly, IL-2 and IL-15 also modulated the TCR-repertoire expressed by developing Treg. Upon transfer into Treg-less Foxp3sf mice, thymus-exit-competent Treg from IL-2- (and to a lesser extent IL-15-) deficient mice suppressed immunopathology less efficiently than wt Treg. Taken together, our results firmly establish important non-redundant quantitative and qualitative roles for IL-2 and, to a lesser extent, IL-15 in intrathymic Treg-development.
2022-08-29 | GSE153484 | GEO
Project description:Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell precursors via the TCR, co-stimulatory receptors, and cytokine receptors. In absence of IL-2, IL-15 or their receptors, fewer Treg apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had recirculated from the periphery back to the thymus, troubling interpretation of these results. We therefore reassessed the involvement of IL-2 and IL-15 in the development of Treg, taking into account Treg-recirculation. At the age of three weeks, when in wt and IL-15-deficient (but not in IL-2-deficient) mice substantial amounts of recirculating Treg are present in the thymus, we found similarly reduced proportions of newly developed Treg in absence of IL-2 or IL-15, and in absence of both cytokines even less Treg developed. In neonates, when practically no recirculating Treg were found in the thymus, the absence of IL-2 led to substantially more reduced Treg-development than deficiency in IL-15. IL-2 but not IL-15 modulated the CD25, GITR, OX40, and CD73-phenotypes of the thymus-egress-competent and periphery-seeding Treg-population. Interestingly, IL-2 and IL-15 also modulated the TCR-repertoire expressed by developing Treg. Upon transfer into Treg-less Foxp3sf mice, newly developed Treg from IL-2- (and to a much lesser extent IL-15-) deficient mice suppressed immunopathology less efficiently than wt Treg. Taken together, our results firmly establish important non-redundant quantitative and qualitative roles for IL-2 and, to a lesser extent, IL-15 in intrathymic Treg-development.
| S-EPMC9495261 | biostudies-literature
Project description:Foxp3 expressing regulatory T cells (Tregs) are the central regulator of immune homeostasis and tolerance. As it is believed that proper Treg function is compromised under inflammatory conditions, exploring a pathway that enhances Treg function is of great importance. In this study, we report that IL-27, an IL-12 family cytokine known to play both pro- and anti-inflammatory role in T cells, plays a pivotal role in Treg function to control T cell-induced colitis. Unlike WT Tregs capable of inhibiting colitogenic T cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T cell responses. Tregs stimulated with IL-27 expressed substantially enhanced suppressive function both in vitro and in vivo. IL-27 stimulation of Tregs induced expression of LAG3, a surface molecule implicated in negatively regulating immune responses. LAG3 expression in IL-27-stimulated Tregs was critical to mediate suppressive Treg function. Finally, human Tregs also displayed enhanced suppressive function and LAG3 expression in response to IL-27 stimulation. Taken together, our results highlight a novel function of the IL-27/LAG3 axis in Treg regulation of inflammatory responses in the intestine. FACS purified Foxp3+ Tregs were stimulated in the presence of media or IL-27 to compare IL-27 induced gene profiles. Four samples (media stimulated or IL-27-stimulated) were collected from four independent experiments. Genes altered by IL-27 treatment were compared to those of media stimulated Tregs.
2015-11-01 | E-GEOD-63455 | biostudies-arrayexpress
Project description:The natures of activation signals are essential in determining T cell subset differentiation, however, the properties of T cell subset preference acquired during intrathymic development remain elusive. Here we show that naïve CD4+ T cells generated in the thymic microenvironment lacking SCD1, the enzyme catalyzing oleic acid production, exhibit enhanced Treg cell differentiation and confer on mice the ability to resist EAE. SCD1 deletion in K14+ thymic epithelia recapitulated the enhanced Treg cell differentiation phenotype of SCD1 knockout mice. The dearth of oleic acid permitted Dot1L to increase H3K79me2 level at the Atp2a2 locus of thymocytes at the DN2-DN3 transition stage. Such epigenetic modification persisted to naïve CD4+ T cells and facilitated Atp2a2 expression. Upon TCR activation, Atp2a2 enhanced the activity of calcium-NFAT1-Foxp3 axis to promote naïve CD4+ T cells to differentiate into Treg cells. Therefore, oleic acid availability is critical for preprogramming thymocytes with Treg differentiation propensities in periphery.
2023-09-29 | GSE237573 | GEO
Project description:Analysis of Foxp3 ablated peripheral regulatory T cells. Regulatory T cells require the expression of the transcription factor Foxp3 for thymic development. It is not known whether continuous expression of Foxp3 is required for the maintained function of mature regulatory T cells in the periphery. Results indicate changes to the regulatory T cell developmental program in the absence of Foxp3. Keywords: genetic modification
2007-01-25 | GSE6681 | GEO
Project description:The natures of activation signals are essential in determining T cell subset differentiation, however, the properties of T cell subset preference acquired during intrathymic development remain elusive. Here we show that naïve CD4+ T cells generated in the thymic microenvironment lacking SCD1, the enzyme catalyzing oleic acid production, exhibit enhanced Treg cell differentiation and confer on mice the ability to resist EAE. SCD1 deletion in K14+ thymic epithelia recapitulated the enhanced Treg cell differentiation phenotype of SCD1 knockout mice. The dearth of oleic acid permitted Dot1L to increase H3K79me2 level at the Atp2a2 locus of thymocytes at the DN2-DN3 transition stage. Such epigenetic modification persisted to naïve CD4+ T cells and facilitated Atp2a2 expression. Upon TCR activation, Atp2a2 enhanced the activity of calcium-NFAT1-Foxp3 axis to promote naïve CD4+ T cells to differentiate into Treg cells. Therefore, oleic acid availability is critical for preprogramming thymocytes with Treg differentiation propensities in periphery.
2023-09-30 | GSE237819 | GEO
Project description:RORγt -expressing FOXP3+ skin-resident Treg cells derived from the periphery in Allergen-Specific Immunotherapy
| PRJNA1058556 | ENA
Project description:Here, we report on experiments in double-transgenic mice, in which RFP is expressed in all Foxp3+ Treg cells, whereas Foxp3-dependent GFP expression is exclusively confined to intrathymically induced Foxp3+ Treg cells. This novel molecular genetic tool enabled us to faithfully track and characterize naturally induced Treg cells of intrathymic (RFP+GFP+) and extrathymic (RFP+GFPM-bM-^HM-^R) origin in otherwise unmanipulated mice. These experiments directly demonstrate that extrathymically induced Treg cells substantially contribute to the overall pool of mature Foxp3+ Treg cells residing in peripheral lymphoid tissues of steady-state mice. Furthermore, we provide evidence that intra- and extrathymically induced Foxp3+ Treg cells represent distinct phenotypic and functional sublineages. CD4+CD25+ RFP+GFP- and CD4+CD25+ RFP+GFP+ T cells from pooled lymph nodes and pooled spleens of 20 mice were FACS sorted for RNA extraction and hybridization on Affymetrix microarrays in duplicates.
2014-07-09 | E-GEOD-59202 | biostudies-arrayexpress
Project description:Overall, we show that IL-34 induced the differentiation of human monocytes with a particular transcriptional profile and these cells favor the development of potent suppressor CD4+ and CD8+ FOXP3+ Tregs.
2020-05-27 | GSE151194 | GEO
Project description:Here, we report on experiments in double-transgenic mice, in which RFP is expressed in all Foxp3+ Treg cells, whereas Foxp3-dependent GFP expression is exclusively confined to intrathymically induced Foxp3+ Treg cells. This novel molecular genetic tool enabled us to faithfully track and characterize naturally induced Treg cells of intrathymic (RFP+GFP+) and extrathymic (RFP+GFP−) origin in otherwise unmanipulated mice. These experiments directly demonstrate that extrathymically induced Treg cells substantially contribute to the overall pool of mature Foxp3+ Treg cells residing in peripheral lymphoid tissues of steady-state mice. Furthermore, we provide evidence that intra- and extrathymically induced Foxp3+ Treg cells represent distinct phenotypic and functional sublineages.
2014-07-09 | GSE59202 | GEO