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2008-D-030-FEL - Abstract

Grant Information

Grant
2008-D-030-FEL
Diabetes - Fellowship
Title
The Role of Plasmacytoid Dendritic Cells in Type 1 Diabetes Mellitus
Investigator
Qing Li, MD, PhD
Institution
Stanford University
Microbiology and Immunology
Funding Status
  • Withdrawn
  • 3 years, $60,000 per year
  • 7/1/2008 to 6/30/2011

Abstract

2008-D-030-FEL - Abstract
Brief Summary
"The Role of Plasmacytoid Dendritic Cells in Type 1 Diabetes Mellitus"

Using gene chips, we have found that the gene expression of a number of genes which are activated by interferon alpha increases sharply between postnatal weeks 2 and 4. This is coincident with the time when large amounts of cellular breakdown products are released in the islets of Langehans by a wave of developmentally programmed cell death (apoptosis) which appears to be a standard feature of early mammalian development of insulin producing β islet cells.

These observations have led to the hypothesis that interferon alpha is the principal initiating factor in the beginning of the diabetic process. If correct, this hypothesis indicates that the initiating process in type 1 diabetes is entirely internal, and is due to a genetically and developmentally programmed wave of beta islet cell death interacting with genes which regulate the immune response in individuals with genes mediating susceptibility to type 1 diabetes.

In order to establish this hypothesis, we successfully blocked the action of type 1 interferons by blocking their receptor with a monoclonal antibody. This treatment not only sharply down-regulated the expression of genes induced by interferon alpha, and blocked the ensuing inflammatory response, which leads to the release of a number of inflammatory cytokines, but also significantly prevented or delayed the onset of T1D. Whether this knowledge can ultimately be applied to developing a prevention for T1D is a matter for further analysis and experimentation on the family of 13 different type 1 interferons which are present in both mouse and man.

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