Poor in vitro maturation and pro-inflammatory cytokine response of dendritic cells in children at genetic risk of type 1 diabetes.
Type 1 diabetes (T1D) has been associated with an aberrant maturation of dendritic cells (DC). We studied the maturation of monocyte-derived DC in children with newly diagnosed T1D and in healthy children with genetic risk for T1D. Peripheral blood monocytes from children with newly diagnosed T1D (n = 12; mean age 13.2 years), children with human leukocyte antigen (HLA)-risk genotype of T1D (n = 7; mean age 12.7 years) and healthy children (n = 14; mean age 11.2 years) were in vitro differentiated into DC. Expression of HLA-DR, CD80/86 and CD11c and secretion of interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, IL-6 and IL-10 were measured using flow cytometry. Lower percentage of DC expressed CD11c and HLA-DR, and decreased production of TNF-alpha was found in children with newly diagnosed T1D and in children at genetic risk when compared to healthy children. Children with risk genotype also had decreased IL-12 production by DC. Children with T1D and children at genetic risk of T1D appear to have similar aberrancies in the maturation of DC, which may predispose to beta-cell autoimmunity.
Skarsvik
S
S
Division of Pediatrics, Department of Molecular and Clinical Medicine, Clinical Research Centre, Linköping University, Linköping, Sweden. susanne.skarsvik@imk.liu.se
Tiittanen
M
M
Lindström
A
A
Casas
R
R
Ludvigsson
J
J
Vaarala
O
O
D018122:B7-1 Antigen / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D009000:Monocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018122:B7-1 Antigen; D039521:CD11c Antigen; D016207:Cytokines; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha