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Interleukin-2 receptor signaling acts as a checkpoint that shapes the distribution of regulatory T cell subsets (RNA-Seq)

ABSTRACT: Regulatory T cells (Tregs) require IL-2 for survival in the periphery, yet how IL-2 shapes Treg heterogeneity remains poorly defined. Here we found that inhibition of IL-2R signaling in post-thymic Tregs leads to a preferential early loss of central Tregs (cTregs). Gene expression of cTregs was more dependent on IL-2R signaling than effector Tregs (eTregs). Unexpectedly, ablation of IL-2R signaling in cTregs resulted in increased proliferation, expression of eTreg genes, and enhanced capacity to develop into eTregs. These findings indicate that physiological amounts of IL-2 act as a checkpoint to maintain cTreg homeostasis and tolerance while restraining their development into eTregs. Nevertheless, direct evaluation of eTregs revealed that loss of IL-2R signaling alters the distribution of eTreg subsets, with increased IFNgR1+ eTregs and CXCR5+ PD-1+ T follicular regulatory (TFR) cells but decreased intestinal RORgt+ TR17 cells. Thus, IL-2R signaling also shapes the development of specialized eTregs subsets.

ORGANISM(S): Mus musculus

PROVIDER: GSE268021 | GEO | 2024/10/18

REPOSITORIES: GEO

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