白细胞介素（IL）-33通过激活调节性T细胞（Treg）来抑制肺部固有的γδT细胞反应，这一成果由美国马萨诸塞州综合医院Andrew D. Luster课题组经过不懈努力而取得。 该研究成果于2020年9月28日发表在《自然-免疫学》上。

研究人员揭示了肺部ST2⁺ Treg细胞在抑制环境过敏原引起的先天免疫应答而不改变适应性免疫应答过程中出人意料的功能。暴露于过敏原后，ST2⁺ Treg细胞被IL-33激活以抑制产生IL-17的γδT细胞。在Treg细胞中ST2信号诱导Ebi3的表达，其是Treg细胞介导的γδT细胞抑制所必需异二聚体细胞因子IL-35的另一个组成部分。这种反应导致诱导嗜酸性粒细胞产生的趋化因子减少，嗜酸性粒细胞向肺的招募减少，这有利于宿主减少过敏原引起的炎症。

因此，该研究确定了肺中ST2⁺ Treg细胞的基本作用，即作为早期先天γδT细胞对粘膜损伤的负调节因子。

据悉，表达IL-33受体ST2的Foxp3⁺调节性T（Treg）细胞相应IL-33参与组织修复。尚不清楚Treg细胞是否也对警报蛋白IL-33产生反应以调节免疫反应的特定方面。

附：英文原文

Title: Interleukin-33 activates regulatory T cells to suppress innate γδ T cell responses in the lung

Author: Lucas D. Faustino, Jason W. Griffith, Rod A. Rahimi, Keshav Nepal, Daniel L. Hamilos, Josalyn L. Cho, Benjamin D. Medoff, James J. Moon, Dario A. A. Vignali, Andrew D. Luster

Issue&Volume: 2020-09-28

Abstract: Foxp3+ regulatory T (Treg) cells expressing the interleukin (IL)-33 receptor ST2 mediate tissue repair in response to IL-33. Whether Treg 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+ Treg cells in suppressing the innate immune response in the lung to environmental allergens without altering the adaptive immune response. Following allergen exposure, ST2+ Treg cells were activated by IL-33 to suppress IL-17-producing γδ T cells. ST2 signaling in Treg cells induced Ebi3, a component of the heterodimeric cytokine IL-35 that was required for Treg 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+ Treg cells in the lung as a negative regulator of the early innate γδ T cell response to mucosal injury.

DOI: 10.1038/s41590-020-0785-3

Source: https://www.nature.com/articles/s41590-020-0785-3