Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development

Meredith O'Keeffe, Thomas C Brodnicki, Ben Fancke, David Vremec, Grant Morahan, Eugene Maraskovsky, Raymond J Steptoe, Leonard C. Harrison, Ken Shortman

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51 Citations (Scopus)


A dendritic cell (DC) imbalance with a marked deficiency in CD4-8+ DC occurs in non-obese diabetic (NOD) mice, a model of human autoimmune diabetes mellitus. Using a NOD congenic mouse strain, we find that this CD4-8+ DC deficiency is associated with a gene segment on chromosome 4, which also encompasses non-MHC diabetes susceptibility loci. Treatment of NOD mice with fms-like tyrosine kinase 3 ligand (FL) enhances the level of CD4-8+ DC, temporarily reversing the DC subtype imbalance. At the same time, fms-like tryosine kinase 3 ligand treatment blocks early stages of the diabetogenic process and with appropriately timed administration can completely prevent diabetes development. This points to a possible clinical use of FL to prevent autoimmune disease.

Original languageEnglish
Pages (from-to)307-314
Number of pages8
JournalInternational Immunology
Issue number3
Publication statusPublished - Mar 2005
Externally publishedYes


  • Autoimmune disease
  • Dendritic cells
  • Diabetes
  • Flt-3 ligand

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