Notch2-dependent GATA3+ Treg cells alleviate allergic rhinitis by suppressing the Th2 cell response

Abstract

The aim of this study was to investigate the role and mechanism of Notch2-dependent GATA3+ Treg cells in allergic rhinitis (AR). Samples were collected from patients in the control and AR groups to detect differences in the numbers of GATA3+ Treg cells and their intracellular Notch2 levels. The effects of Notch2 on GATA3+ Treg cell differentiation and function in vitro were detected. AR mice were subjected to adoptive transfer of GATA3+ Treg cells to detect changes in the allergic inflammatory response and Th2 cells. Mice with Treg cell-specific knockout of Notch2 were constructed, and an AR model was established to detect the changes. The number of GATA3+ Treg cells and intracellular Notch2 expression in peripheral blood of the AR group were decreased compared with the controls (P < 0.05), and the number of GATA3+ Treg cells was significantly negatively correlated with the level of allergen-specific IgE (sIgE; P < 0.01). In vitro experiments showed that Notch2 promoted the differentiation and immunosuppressive function of GATA3+ Treg cells, and Notch2 directly promoted GATA3 transcription in Treg cells (P < 0.05). Animal experiments indicated that adoptive transfer of GATA3+ Treg cells reduced the allergic inflammatory response in AR mice (P < 0.05). The number of GATA3+ Treg cells was decreased in gene knockout mice (P < 0.05), and autoimmune inflammation was observed. After modeling, the allergic inflammatory response was further aggravated (P < 0.05). Overall, our findings indicate that Notch2 alleviates AR by specifically increasing GATA3+ Treg cell differentiation. Notch2 expressed in Treg cells is expected to be a new therapeutic target for AR.