| 1 | Efficient IL-2R signaling differentially affects the stability,function,and composition of the regulatory T-cell pool显示文摘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,theα-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,Cd25^(Y^(129H))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. | Marc Permanyer Berislav Bošnjak Silke Glage Michaela Friedrichsen Stefan Floess Jochen Huehn Gwendolyn E.Patzer Ivan Odak Nadine Eckert Razieh Zargari Laura Ospina-Quintero Hristo Georgiev Reinhold Förster | 2021 | Cellular & Molecular Immunology2021，18，2： | 2 |
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