期刊
ENDOCRINOLOGY
卷 159, 期 11, 页码 3834-3847出版社
ENDOCRINE SOC
DOI: 10.1210/en.2018-00649
关键词
-
资金
- Canadian National Transplant Research Program
- McGill University Health Centre Foundation (Royal Victoria Hospital)
The autoimmune response that characterizes type 1 diabetes (T1 D) has no clear cause. Extracellular vesicles (EVs) play an important role in triggering the immune response in other contexts. Here, we propose a model by which EVs isolated from human islets stimulate proinflammatory immune responses and lead to peripheral blood mononuclear cell (PBMC) activation. We show that human islet EVs are internalized by monocytes and B cells and lead to an increase in T-helper 1, 2, and 17 cytokine expression, as well as T and B cell proliferation. Importantly, we demonstrate memory T and B cell activation by EVs selectively in PBMCs of patients with T1D. Additionally, human islet EVs induce an increase in antibodies against glutamic acid decarboxylase 65 (GAD65) in T1D PBMCs. Furthermore, pretreatment of T1D PBMCs with ibrutinib, an inhibitor of Bruton tyrosine kinase, dampens EV-induced memory B cell activation and GAD65 antibody production. Collectively, our findings indicate a role for human islet EVs in mediating activation of B and T cells and GAD65 autoantibody production.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据