Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610;
Department of Pediatrics, University of Florida, Gainesville, FL 32610; and.
J Immunol. 2014 Aug 1;193(3):1024-34. doi: 10.4049/jimmunol.1303230. Epub 2014 Jun 27.
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.
越来越多的证据表明，I 型干扰素（IFN-αβ）与 Th1 介导的 1 型糖尿病（T1D）的发病机制有关。I 型干扰素的主要来源是浆细胞样树突状细胞（pDCs）。在这项研究中，我们分析了处于危险中的、新发病的和已确诊的 T1D 患者和对照者的外周血 pDC 数量和功能。我们发现，与对照者相比，处于 T1D 发病风险中的、新发病的和已确诊的 T1D 患者具有显著增加的 pDCs，但髓样树突状细胞数量相似。在 T1D 患者中，pDC 数量不受年龄的影响，但在对照者中随年龄增长而下降。结果表明，流感病毒刺激的 PBMCs 产生的 IFN-α在 T1D 患者中明显高于对照者，并且 IFN-α的产生与 PBMCs 中的 pDC 数量相关。有趣的是，只有 T1D 相关的柯萨奇病毒 B4 型而不是 B3 型诱导大多数 T1D PBMC 产生 IFN-α，这被证实是由 pDCs 分泌的。最后，体外研究表明，pDC 产生的 IFN-α增强了 Th1 反应，来自 T1D 患者的 IFN-γ产生的 CD4(+)T 细胞显著增加。这些发现表明，增加的 pDCs 及其 IFN-αβ 的产生可能与这种 Th1 介导的自身免疫性疾病有关，尤其是在与 T1D 发病机制相关的某些病毒感染下。
