Essential and non-overlapping IL-2Rα-dependent processes for thymic development and peripheral homeostasis of regulatory T cells

Kevin H. Toomer, Jen Bon Lui, Norman H. Altman, Yuguang Ban, Xi Chen and Thomas R. Malek ()
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Kevin H. Toomer: University of Miami
Jen Bon Lui: University of Miami
Norman H. Altman: University of Miami
Yuguang Ban: University of Miami
Xi Chen: University of Miami
Thomas R. Malek: University of Miami

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract IL-2R signaling is essential for regulatory T cell (Treg) function. However, the precise contribution of IL-2 during Treg thymic development, peripheral homeostasis and lineage stability remains unclear. Here we show that IL-2R signaling is required by thymic Tregs at an early step for expansion and survival, and a later step for functional maturation. Using inducible, conditional deletion of CD25 in peripheral Tregs, we also find that IL-2R signaling is indispensable for Treg homeostasis, whereas Treg lineage stability is largely IL-2-independent. CD25 knockout peripheral Tregs have increased apoptosis, oxidative stress, signs of mitochondrial dysfunction, and reduced transcription of key enzymes of lipid and cholesterol biosynthetic pathways. A divergent IL-2R transcriptional signature is noted for thymic Tregs versus peripheral Tregs. These data indicate that IL-2R signaling in the thymus and the periphery leads to distinctive effects on Treg function, while peripheral Treg survival depends on a non-conventional mechanism of metabolic regulation.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08960-1

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DOI: 10.1038/s41467-019-08960-1

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