Foxp3⁺ regulatory T (T_reg) cells expressing the interleukin (IL)-33 receptor ST2 mediate tissue repair in response to IL-33. Whether T_reg cells also respond to the alarmin IL-33 to regulate specific aspects of the immune response is not known. Here we describe an unexpected function of ST2⁺ T_reg cells in suppressing the innate immune response in the lung to environmental allergens without altering the adaptive immune response. Following allergen exposure, ST2⁺ T_reg cells were activated by IL-33 to suppress IL-17-producing γδ T cells. ST2 signaling in T_reg cells induced Ebi3, a component of the heterodimeric cytokine IL-35 that was required for T_reg cell-mediated suppression of γδ T cells. This response resulted in fewer eosinophil-attracting chemokines and reduced eosinophil recruitment into the lung, which was beneficial to the host in reducing allergen-induced inflammation. Thus, we define a fundamental role for ST2⁺ T_reg cells in the lung as a negative regulator of the early innate γδ T cell response to mucosal injury.

表达白介素 (IL)-33 受体 ST2 的Foxp3 ⁺调节性 T (T _reg ) 细胞介导响应 IL-33 的组织修复。T _reg细胞是否也对警报素 IL-33 作出反应以调节免疫反应的特定方面尚不清楚。在这里，我们描述了 ST2 ⁺ T _reg细胞在抑制肺部对环境过敏原的先天免疫反应而不改变适应性免疫反应方面的意外功能。过敏原暴露后，ST2 ⁺ T _reg细胞被 IL-33 激活以抑制产生 IL-17 的 γδ T 细胞。_{T reg}中的 ST2 信号传导细胞诱导 Ebi3，这是 T _reg细胞介导的 γδ T 细胞抑制所必需的异二聚细胞因子 IL-35 的成分。这种反应导致较少的嗜酸性粒细胞吸引趋化因子和减少嗜酸性粒细胞向肺的募集，这有利于宿主减少过敏原引起的炎症。因此，我们将肺中ST2 ⁺ T _reg细胞的基本作用定义为早期先天性 γδ T 细胞对粘膜损伤反应的负调节剂。