期刊
CLINICAL IMMUNOLOGY
卷 140, 期 1, 页码 3-7出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2011.04.010
关键词
IFN-alpha; Plasmacytoid DC; Type 1 diabetes
类别
资金
- Juvenile Diabetes Research Foundation (JDRF) [2007-745]
- Larry L. Hillblom Foundation [2008-D-030-FEL]
Type 1 diabetes (T1D) is an autoimmune disease in both humans and the nonobese diabetic (NOD) mouse, in which the insulin-producing-cells of the pancreatic islets are destroyed by a beta islet cell-specific T cell immune response. We recently reported that interferon (IFN)-alpha is an early trigger of the T1D process in NOD mice. Here, we show that extensive blockade of IFN-alpha action by a monoclonal antibody specific to IFN-alpha receptor 1 results in nearly complete prevention of T1D in NOD mice. Whether professional IFN-alpha producing cells, plasmacytoid dendritic cells (pDCs), are responsible for the initiation of T1D has been unclear. Here we demonstrate that depletion of pDCs in NOD mice by a specific mAb given at 15-25 days of age significantly delays the onset and decreases the incidence of T1D. These findings indicate that pDC and pDC-derived IFN-alpha are the prime initiators of the pathogenesis of T1D in NOD mice. (C) 2011 Elsevier Inc. All rights reserved.
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