Regulatory T (Treg) cells maintain immune homeostasis by limiting autoimmune and inflammatory responses. Treg differentiation, maintenance, and function are controlled by the transcription factor Foxp3. However, the exact molecular mechanisms underlying Treg cell regulation remain elusive. Here, we show that Treg cell–specific ablation of the E3 ubiquitin ligase Itch in mice caused massive multiorgan lymphocyte infiltration and skin lesions, chronic T cell activation, and the development of severe antigen-induced airway inflammation. Surprisingly, Foxp3 expression, homeostasis, and the in vitro and in vivo suppressive capability of Treg cells were not affected by Itch deficiency. We found that the expression of Th2 cytokines by Treg cells was increased in the absence of Itch. Fate mapping revealed that a fraction of Treg cells lost Foxp3 expression independently of Itch. However, Th2 cytokines were excessively augmented in
Hyung-seung Jin, Yoon Park, Chris Elly, Yun-Cai Liu
Itch-deficient Treg cells instruct the differentiation of naive T cells into Th2 in vitro.