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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.

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