The role of interferon alpha in initiation of type I diabetes in the NOD mouse

Clin Immunol. 2011 Jul;140(1):3-7. doi: 10.1016/j.clim.2011.04.010. Epub 2011 Apr 22.

Abstract

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)-α is an early trigger of the T1D process in NOD mice. Here, we show that extensive blockade of IFN-α action by a monoclonal antibody specific to IFN-α receptor 1 results in nearly complete prevention of T1D in NOD mice. Whether professional IFN-α 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-α are the prime initiators of the pathogenesis of T1D in NOD mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells / immunology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Interferon-alpha / immunology*
  • Mice
  • Mice, Inbred NOD

Substances

  • Interferon-alpha