Decreased dendritic cell numbers but increased TLR9-mediated interferon-alpha production in first degree relatives of type 1 diabetes patients

被引:20
|
作者
Kayserova, Jana [1 ]
Vcelakova, Jana [2 ]
Stechova, Katerina [2 ]
Dudkova, Eva [1 ]
Hromadkova, Hana [1 ]
Sumnik, Zdenek [2 ]
Kolouskova, Stanislava [2 ]
Spisek, Radek [1 ,3 ]
Sediva, Anna [1 ]
机构
[1] Charles Univ Prague, Univ Hosp Motol, Fac Med 2, Dept Immunol, Prague 15006, Czech Republic
[2] Charles Univ Prague, Univ Hosp Motol, Fac Med 2, Dept Pediat, Prague 15006, Czech Republic
[3] Sotio As, Prague, Czech Republic
关键词
Dendritic cell; Interferon-alpha; Type; 1; diabetes; PERIPHERAL-BLOOD; INNATE IMMUNITY; T-CELLS; MICE; CROSSTALK; INDUCTION; MOLECULES; FREQUENCY; DISEASE; MOUSE;
D O I
10.1016/j.clim.2014.03.018
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: Dendritic cells (DCs) play an important role in pathogenesis of autoimmunity, including type 1 diabetes (T1D). In this study, we investigated DC subpopulations and their responses to TLR stimulation in T1D patients and their relatives. Methods: We analyzed the frequency of myeloid (mDCs) and plasmacytoid DCs (pDCs) in 97 T1D patients (69 onset, 28 long-term), 67 first-degree relatives, and 64 controls. We additionally tested the IFN-alpha production by pDCs upon stimulation with TLR 7, 8 and 9 agonists. Results: A lower number of mDCs and pDCs were found in T1D patients and their relatives. Of all the tested TLR ligands, only stimulation with CpG 2216 induced IFN-alpha production that was the highest in T1D relatives, except of autoantibody-negative relatives bearing the protective haplotypes. Conclusion: Our data demonstrate disturbances in DC number and function expressed most significantly in T1D relatives and point to a potential role of TLR9-induced IFN-alpha production in T1D development. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:49 / 55
页数:7
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