1 型糖尿病从糖尿病前期阶段进展受到干扰素-α信号的控制。
Progression of type 1 diabetes from the prediabetic stage is controlled by interferon-α signaling.
机构信息
Department of Immunology & Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom.
出版信息
Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):3708-3713. doi: 10.1073/pnas.1700878114. Epub 2017 Mar 21.
Abstract
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 -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 , and , thereby limiting their killing ability. By such means, insulin production was preserved and glucose regulation maintained, and a mechanism for S1PR1 immunomodulation described.
摘要
使用抗体或选择性 S1PR1 激动剂 CYM-5442 阻断 IFN-α而不是 IFN-β信号通路，可预防小鼠 -LCMV T1D 模型中的 1 型糖尿病（T1D）。首先，抗体或 CYM-5442 的治疗限制了自身免疫性“抗自身”T 细胞向胰岛周围外部边界的迁移，并阻止其进入胰岛，从而无法定位、杀伤，从而消除胰岛素产生的β细胞。其次，CYM-5442 通过上调负免疫调节受体基因和，诱导抗自身 T 细胞衰竭特征，从而限制其杀伤能力。通过这种方式，胰岛素的产生得到了保留，葡萄糖的调节得以维持，并描述了 S1PR1 免疫调节的一种机制。
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