文章基本信息

标题：Progression of type 1 diabetes from the prediabetic stage is controlled by interferon-α signaling
本地全文：下载
作者：Brett S. Marro ; Brian C. Ware ; Jaroslav Zak 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：14
页码：3708-3713
DOI：10.1073/pnas.1700878114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Blockade of IFN-α but not IFN-β signaling using either an antibody or a selective S1PR1 agonist, CYM-5442, prevented type 1 diabetes (T1D) in the mouse Rip -LCMV T1D model. First, treatment with antibody or CYM-5442 limited the migration of autoimmune “antiself” T cells to the external boundaries around the islets and prevented their entry into the islets so they could not be positioned to engage, kill, and thus remove insulin-producing β cells. Second, CYM-5442 induced an exhaustion signature in antiself T cells by up-regulating the negative immune regulator receptor genes Pdcd1, Lag3, Ctla4, Tigit , and Btla , thereby limiting their killing ability. By such means, insulin production was preserved and glucose regulation maintained, and a mechanism for S1PR1 immunomodulation described.
关键词：type I interferon ; IFN-alpha ; S1PR1 ; type 1 diabetes