文章基本信息

标题：Treg-specific IL-27Rα deletion uncovers a key role for IL-27 in Treg function to control autoimmunity
本地全文：下载
作者：Jeongsu Do ; Dongkyun Kim ; Sohee Kim 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：38
页码：10190-10195
DOI：10.1073/pnas.1703100114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Dysregulated Foxp3⁺ Treg functions result in uncontrolled immune activation and autoimmunity. Therefore, identifying cellular factors modulating Treg functions is an area of great importance. Here, using Treg-specific Il27ra ^−/− mice, we report that IL-27 signaling in Foxp3⁺ Tregs is essential for Tregs to control autoimmune inflammation in the central nervous system (CNS). Following experimental autoimmune encephalomyelitis (EAE) induction, Treg-specific Il27ra ^−/− mice develop more severe EAE. Consistent with the severe disease, the numbers of IFNγ- and IL-17–producing CD4 T cells infiltrating the CNS tissues are greater in these mice. Treg accumulation in the inflamed CNS tissues is not affected by the lack of IL-27 signaling in Tregs, suggesting a functional defect of Il27ra ^−/− Tregs. IL-10 production by conventional CD4 T cells and their CNS accumulation are rather elevated in Treg-specific Il27ra ^−/− mice. Analysis with Treg fate-mapping reporter mice further demonstrates that IL-27 signaling in Tregs may control stability of Foxp3 expression. Finally, systemic administration of recombinant IL-27 in Treg-specific Il27ra ^−/− mice fails to ameliorate the disease even in the presence of IL-27–responsive conventional CD4 T cells. These findings uncover a previously unknown role of IL-27 in regulating Treg function to control autoimmune inflammation.
关键词：autoimmunity ; Foxp3+ regulatory T cells ; IL-27 ; Tr1 cells