title: Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development.
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 tyrosine 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.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
authors.forename: Meredith
authors.initials: M
authors.lastname: O'Keeffe
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Brodnicki
authors.forename: Ben
authors.initials: B
authors.lastname: Fancke
authors.forename: David
authors.initials: D
authors.lastname: Vremec
authors.forename: Grant
authors.initials: G
authors.lastname: Morahan
authors.forename: Eugene
authors.initials: E
authors.lastname: Maraskovsky
authors.forename: Raymond
authors.initials: R
authors.lastname: Steptoe
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Harrison
authors.forename: Ken
authors.initials: K
authors.lastname: Shortman
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006801:Humans; D008565:Membrane Proteins / Q000627:therapeutic use*; D051379:Mice; D016688:Mice, Inbred NOD; D009154:Mutation
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D008565:Membrane Proteins; C084881:flt3 ligand protein