研究揭示白細胞介素33抑制肺部固有γδT細胞反應的機制
作者：
小柯機器人發布時間：2020/9/30 15:12:43
白細胞介素（IL）-33通過激活調節性T細胞（Treg）來抑制肺部固有的γδT細胞反應，這一成果由美國麻薩諸塞州綜合醫院Andrew D. Luster課題組經過不懈努力而取得。 該研究成果於2020年9月28日發表在《自然-免疫學》上。
研究人員揭示了肺部ST2+ Treg細胞在抑制環境過敏原引起的先天免疫應答而不改變適應性免疫應答過程中出人意料的功能。暴露於過敏原後，ST2+ Treg細胞被IL-33激活以抑制產生IL-17的γδT細胞。在Treg細胞中ST2信號誘導Ebi3的表達，其是Treg細胞介導的γδT細胞抑制所必需異二聚體細胞因子IL-35的另一個組成部分。這種反應導致誘導嗜酸性粒細胞產生的趨化因子減少，嗜酸性粒細胞向肺的招募減少，這有利於宿主減少過敏原引起的炎症。
因此，該研究確定了肺中ST2+ Treg細胞的基本作用，即作為早期先天γδT細胞對黏膜損傷的負調節因子。
據悉，表達IL-33受體ST2的Foxp3+調節性T（Treg）細胞相應IL-33參與組織修復。尚不清楚Treg細胞是否也對警報蛋白IL-33產生反應以調節免疫反應的特定方面。
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