title: Increased IFN-α-producing plasmacytoid dendritic cells (pDCs) in human Th1-mediated type 1 diabetes: pDCs augment Th1 responses through IFN-α production.
abstract: Increasing evidence suggests that type 1 IFN (IFN-αβ) is associated with pathogenesis of Th1-mediated type 1 diabetes (T1D). A major source of IFN-αβ is plasmacytoid dendritic cells (pDCs). In this study, we analyzed peripheral blood pDC numbers and functions in at-risk, new-onset, and established T1D patients and controls. We found that subjects at risk for T1D and new-onset and established T1D subjects possessed significantly increased pDCs but similar number of myeloid DCs when compared with controls. pDC numbers were not affected by age in T1D subjects but declined with increasing age in control subjects. It was demonstrated that IFN-α production by PBMCs stimulated with influenza viruses was significantly higher in T1D subjects than in controls, and IFN-α production was correlated with pDC numbers in PBMCs. Of interest, only T1D-associated Coxsackievirus serotype B4 but not B3 induced majority of T1D PBMCs to produce IFN-α, which was confirmed to be secreted by pDCs. Finally, in vitro studies demonstrated IFN-α produced by pDCs augmented Th1 responses, with significantly greater IFN-γ-producing CD4(+) T cells from T1D subjects. These findings indicate that increased pDCs and their IFN-αβ production may be associated with this Th1-mediated autoimmune disease, especially under certain viral infections linked to T1D pathogenesis.
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610;
authors: Chang-Qing
authors: CQ
authors: Xia
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610;
authors: Ruihua
authors: R
authors: Peng
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610;
authors: Anna V
authors: AV
authors: Chernatynskaya
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610;
authors: Lihui
authors: L
authors: Yuan
authors: Department of Pediatrics, University of Florida, Gainesville, FL 32610; and.
authors: Carolyn
authors: C
authors: Carter
authors: Department of Medicine, University of Florida, Gainesville, FL 32610.
authors: John
authors: J
authors: Valentine
authors: Department of Medicine, University of Florida, Gainesville, FL 32610.
authors: Eric
authors: E
authors: Sobel
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610;
authors: Mark A
authors: MA
authors: Atkinson
authors: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610; salzler@pathology.ufl.edu.
authors: Michael J
authors: MJ
authors: Clare-Salzler
mesh_terms: D000293:Adolescent; D000328:Adult; D001772:Blood Cell Count; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D007223:Infant; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D009975:Orthomyxoviridae / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015854:Up-Regulation / Q000276:immunology*; D055815:Young Adult
chemical_list: D016898:Interferon-alpha