美国马萨诸塞州总医院Andrew D. Luster及其研究组发现，来源于调节性T（T_reg）细胞的IL-1Ra可抑制由呼吸道病毒感染引起的先天免疫反应。这一研究成果于2023年11月9日发表在国际学术期刊《自然-免疫学》上。

研究人员发现敲除Treg细胞上的白细胞介素（IL）-33受体ST2会导致粒细胞流入肺部增多，并诱导先天性淋巴细胞和γδ T细胞产生的细胞因子增加，而不会改变对流感的适应性免疫。IL-33在ST2⁺ T_reg细胞中诱导高水平的白细胞介素-1受体拮抗剂（IL-1Ra），而在T_reg细胞中敲除IL-1Ra会增加粒细胞流入肺部。T_reg细胞特异性缺失ST2或IL-1Ra可提高流感病毒的存活率，这取决于IL-1。肺内基底成纤维细胞表达高水平的IL-1受体，T_reg细胞产生的IL-1Ra会抑制其趋化因子的产生。因此，研究人员揭示了一种新的调控路径，即组织T_reg细胞产生的IL-33会诱导IL-1Ra，其可抑制由IL-1介导的由呼吸道病毒感染引起的先天免疫反应。

据介绍，已有研究充分揭示了调节性T细胞对适应性免疫和组织稳态的调节作用；然而，人们对Treg细胞介导的先天性免疫反应调节作用却知之甚少。

附：英文原文

Title: Regulatory T cell-derived IL-1Ra suppresses the innate response to respiratory viral infection

Author: Griffith, Jason W., Faustino, Lucas D., Cottrell, Victoria I., Nepal, Keshav, Hariri, Lida P., Chiu, Rebecca Suet-Yan, Jones, Michael C., Jul, Amlie, Gabay, Cem, Luster, Andrew D.

Issue&Volume: 2023-11-09

Abstract: Regulatory T (Treg) cell modulation of adaptive immunity and tissue homeostasis is well described; however, less is known about Treg cell-mediated regulation of the innate immune response. Here we show that deletion of ST2, the receptor for interleukin (IL)-33, on Treg cells increased granulocyte influx into the lung and increased cytokine production by innate lymphoid and γδ T cells without alteration of adaptive immunity to influenza. IL-33 induced high levels of the interleukin-1 receptor antagonist (IL-1Ra) in ST2+ Treg cells and deletion of IL-1Ra in Treg cells increased granulocyte influx into the lung. Treg cell-specific deletion of ST2 or IL-1Ra improved survival to influenza, which was dependent on IL-1. Adventitial fibroblasts in the lung expressed high levels of the IL-1 receptor and their chemokine production was suppressed by Treg cell-produced IL-1Ra. Thus, we define a new pathway where IL-33-induced IL-1Ra production by tissue Treg cells suppresses IL-1-mediated innate immune responses to respiratory viral infection. Luster and colleagues report that lung-resident ST2+ regulatory T cells secrete the IL-1 antagonist IL-1Ra to suppress neutrophils and early innate immune responses to influenza virus infection.

DOI: 10.1038/s41590-023-01655-2

Source: https://www.nature.com/articles/s41590-023-01655-2