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Efficient IL-2R signaling differentially affects stability, function, and composition of the regulatory T cell pool

ABSTRACT: Efficient IL-2R signaling differentially affects stability, function, and composition of the regulatory T cell pool

PROVIDER: PRJNA677933 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13043762_1.fastq.gz	Fastqsanger.gz
	SRR13043762_2.fastq.gz	Fastqsanger.gz
	SRR13043763_1.fastq.gz	Fastqsanger.gz
	SRR13043763_2.fastq.gz	Fastqsanger.gz
	SRR13043764_1.fastq.gz	Fastqsanger.gz

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Efficient IL-2R signaling differentially affects stability, function, and composition of the regulatory T cell pool

Project description:Signaling via the interleukin 2 receptor (IL-2R) is a requisite for Treg cell identity and function. However, it is not completely understood to what degree IL-2R signaling is required for Treg cell homeostasis, lineage stability and function during both resting and inflammatory conditions. Here, we characterized a spontaneous mouse mutant endowed with a hypomorphic Tyr129His variant of CD25, the a chain of the IL 2R, which resulted in diminished receptor expression and reduced IL-2R signaling. Under non-inflammatory conditions Cd25-Y129H mice harbored substantially lower numbers of peripheral Treg cells with stable Foxp3 expression that prevented the development of spontaneous autoimmune diseases. In contrast, Cd25-Y129H Treg cells failed to efficiently induce immune suppression and lost linage commitment in a T cell transfer colitis model, indicating that unimpaired IL-2R signaling is critical for Treg cell function in inflammatory environments. Moreover, single-cell RNA sequencing of Treg cells revealed that impaired IL-2R signaling profoundly affected the balance of central and effector Treg cell subsets. Thus, partial loss of IL-2R signaling differentially interferes with maintenance, heterogeneity and suppressive function of the regulatory T cell pool.

2021-01-15 | GSE161345 | GEO

Efficient IL-2R signaling differentially affects the stability, function, and composition of the regulatory T-cell pool.

Project description:Signaling via interleukin-2 receptor (IL-2R) is a requisite for regulatory T (Treg) cell identity and function. However, it is not completely understood to what degree IL-2R signaling is required for Treg cell homeostasis, lineage stability and function in both resting and inflammatory conditions. Here, we characterized a spontaneous mutant mouse strain endowed with a hypomorphic Tyr129His variant of CD25, the α-chain of IL-2R, which resulted in diminished receptor expression and reduced IL-2R signaling. Under noninflammatory conditions, Cd25Y129H mice harbored substantially lower numbers of peripheral Treg cells with stable Foxp3 expression that prevented the development of spontaneous autoimmune disease. In contrast, Cd25Y129H Treg cells failed to efficiently induce immune suppression and lost lineage commitment in a T-cell transfer colitis model, indicating that unimpaired IL-2R signaling is critical for Treg cell function in inflammatory environments. Moreover, single-cell RNA sequencing of Treg cells revealed that impaired IL-2R signaling profoundly affected the balance of central and effector Treg cell subsets. Thus, partial loss of IL-2R signaling differentially interferes with the maintenance, heterogeneity, and suppressive function of the Treg cell pool.

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Analysis of gene expression in Df(2R)ED3921 (hmgd/z deficiency) and Df(2R)ED50000 (hmgd deficiency) strains

Project description:We analysed the effect of the deficiency Df(2R)ED3921 and Df(2R)ED50000 on gene expression in embryos (stage 0-11), and wing imaginal discs and brains from 3rd instar larvae. Df(2R)ED3921 and Df(2R)ED50000 were described in Ragab et al. (2005) Genetics 172:1069-1078 2005. RNA from Df(2R)ED3921 and Df(2R)ED50000 embryos was compared to a pool of RNA extracted from wild-type embryos at the same stage. For each genotype, 4 independent biological replicates were performed (2 of these dyes swapped with respect to the other two). The same experimental protocol and genotypes were used for the analysis in dissected wing imaginal discs and brains from 3rd instar larvae.

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Streptomyces sp. 2R strain:2R

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Pantoea sp. MBD-2R isolate:MBD-2R

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Project description:Differentiation and homeostasis of Foxp3 + regulatory T cells (Tregs) are tightly controlled by the interleukin-2 receptor (IL-2R) signaling, yet the mechanisms governing these processes are incompletely understood. Here we report that transcription factor Bach2 attenuates IL-2R signaling to coordinate Treg differentiation and homeostasis by directly repressed CD25 (IL-2Rα). Thus, Bach2 balances IL-2R signaling to orchestrate development and homeostasis of various Treg subsets.

2021-05-11 | GSE164937 | GEO

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Drosophila 16-20 hrs embryos: DHR3G60S/Df(2R)12 vs. w1118

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Negative Elongation Factor (NELF) regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation [RNAseq_48hrs]

Project description:Negative Elongation Factor (NELF) is a critical transcriptional regulator that works through stabilizing paused RNA Polymerase to permit rapid gene expression changes in response to environmental cues. Whilst NELF is essential for embryonic development, its role in adult stem cells remains unclear. Here, through a muscle stem cell-specific deletion, we show that NELF is required for efficient muscle regeneration and replenishing the stem cell pool. Mechanistic studies using PRO-seq, single cell trajectory analyses and myofiber cultures revealed that NELF works at a specific stage of muscle regeneration whereby it mediates massive expansion of muscle progenitors. Strikingly, transplantation experiments indicate that these progenitors are also necessary for stem cell pool repopulation implying they are able to return to quiescence. Thus, we identified a critical role for NELF in expansion of muscle progenitors in response to injury and revealed that progenitors returning to quiescence are major contributors to stem cell pool repopulation.

2021-03-18 | GSE162775 | GEO

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