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Dynamic transcriptional activity and chromatin remodeling of regulatory T cells after varied duration of IL-2R signaling [RNA-seq]

ABSTRACT: Regulatory T cells (Tregs) are necessary for the maintenance of immune self-tolerance and homeostasis. They have a heightened sensitivity to IL-2, which may create a therapeutic window to promote immune regulation by their selective stimulation. While IL-2 responsive genes are well characterized, yet remain unknown genetic, chromatin and metabolic programs during sustained IL-2R signaling. Longitudinal transcriptional and chromatin accessibility profiling and metabolic studies were performed on peripheral Tregs in response to long-lived mIL-2/CD25 fusion protein. We found an initially increased STAT5 dependent gene modulation enabled by enhanced chromatin accessibility, whereas a STAT5-independent genome-wide chromatin closing to inhibit transcription and cell signaling occurred later. Interestingly, IL-2-dependent genes were induced upon re-stimulation. Mitochondrial metabolism was reprogrammed to fulfill the bioenergetics demand for the burst of proliferation. We propose that a shift from euchromatin to heterochromatin represents a mechanism to restrain, but not abrogate, persistent IL-2R signaling to maintain Treg homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE163946 | GEO | 2022/02/16

REPOSITORIES: GEO

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Dynamic transcriptional activity and chromatin remodeling of regulatory T cells after varied duration of IL-2R signaling

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