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

O'Keeffe, Meredith, Brodnicki, Thomas C., Fancke, Ben, Vremec, David, Morahan, Grant, Maraskovsky, Eugene, Steptoe, Raymond, Harrison, Leonard C. and Shortman, Ken (2005) Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development. International Immunology, 17 3: 307-314. doi:10.1093/intimm/dxh210


Author O'Keeffe, Meredith
Brodnicki, Thomas C.
Fancke, Ben
Vremec, David
Morahan, Grant
Maraskovsky, Eugene
Steptoe, Raymond
Harrison, Leonard C.
Shortman, Ken
Title Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development
Journal name International Immunology   Check publisher's open access policy
ISSN 0953-8178
Publication date 2005
Sub-type Article (original research)
DOI 10.1093/intimm/dxh210
Volume 17
Issue 3
Start page 307
End page 314
Total pages 8
Place of publication Oxford
Publisher Oxford University Press
Language eng
Subject 270100 Biochemistry and Cell Biology
Abstract 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.
Keyword Immunology
Autoimmune Disease
Dendritic Cells
Diabetes
Flt-3 Ligand
Cd4 T-cells
In-vivo
Flt3 Ligand
Biological-activity
Interleukin (il)-4
Ifn-gamma
Mouse
Tolerance
Subsets
Cd8(+)
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
UQ Diamantina Institute Publications
 
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Created: Mon, 13 Aug 2007, 15:01:11 EST