IL‐2Rβ links IL‐2R signaling with Foxp3 expression

Abstract

Immunological tolerance to self antigens is a tightly regulated process. Recent work has demonstrated that the forkhead family member Foxp3 is a critical element in the differentiation and function of mouse CD4⁺CD25⁺ regulatory T cells (Treg). Recent work has suggested an important role for IL‐2 in the development and maintenance of Treg. To directly assess the effect of IL‐2 signaling on Treg development and function, we analyzed mice that were genetically deficient in components of the IL‐2 receptor (IL‐2R). Mice lacking CD25 (IL‐2Rα) displayed a slight decrease in Treg within the thymus, while peripheral numbers are unchanged. In contrast, we found that mice deficient in CD122 (IL‐2Rβ) had a profound reduction in both thymic and peripheral Treg, coinciding with more rapid development of a fatal lymphoproliferative disease. Expression of a Foxp3 transgene restored Treg and protected against the onset of autoimmunity. Thus, a signal mediated by IL‐2Rβ is essential for the development and homeostasis of Foxp3⁺ Treg in vivo.