Abstract
Abstract Maintenance of regulatory T (Treg) cells is crucial for the regulatory function of Treg cells in immune homeostasis and self-tolerance; however, the detailed mechanisms remain elusive. In this study, we found that the cytokine suppressor CIS is required for maintenance of Treg identity. Mice with Treg specific Cis-deficiency displayed aggravated experimental allergic asthma and in adulthood, developed splenomegaly, lymphadenopathy and spontaneous eosinophilic airway inflammation, accompanied by accumulation of memory T helper (TH) cells. Cis-deficiency led to decreased expression of Foxp3 and suppressive function of Treg cells. Cis-deficient Treg cells expressed TH2 signature genes, Gata3, Irf4 and Il4, and excessive IL-4-STAT6 signals resulted in repressive chromatin modification in the Foxp3 locus and permissive modification in the Il4 loci. In vitro, blockade of IL-4 restored expression of Foxp3 and suppressive function of iTreg cells. Thus, we identified a novel feedback loop in stabilization of Treg cells and inhibition of TH2 type inflammation.
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