PMID- 24709112 OWN - NLM STAT- MEDLINE DCOM- 20140912 LR - 20140614 IS - 1521-7035 (Electronic) IS - 1521-6616 (Linking) VI - 153 IP - 1 DP - 2014 Jul TI - Decreased dendritic cell numbers but increased TLR9-mediated interferon-alpha production in first degree relatives of type 1 diabetes patients. PG - 49-55 LID - S1521-6616(14)00082-5 [pii] LID - 10.1016/j.clim.2014.03.018 [doi] AB - 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. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Kayserova, Jana AU - Kayserova J AD - Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, V Uvalu 84, Prague, Czech Republic. Electronic address: jana.kayserova@lfmotol.cuni.cz. FAU - Vcelakova, Jana AU - Vcelakova J AD - Department of Pediatrics, Charles University, 2nd Faculty of Medicine, University Hospital Motol, V Uvalu 84, Prague, Czech Republic. Electronic address: jana.vcelakova@lfmotol.cuni.cz. FAU - Stechova, Katerina AU - Stechova K AD - Department of Pediatrics, Charles University, 2nd Faculty of Medicine, University Hospital Motol, V Uvalu 84, Prague, Czech Republic. Electronic address: katerina.stechova@lfmotol.cuni.cz. FAU - Dudkova, Eva AU - Dudkova E AD - Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, V Uvalu 84, Prague, Czech Republic. Electronic address: eva.dudkova@fnmotol.cz. FAU - Hromadkova, Hana AU - Hromadkova H AD - Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, V Uvalu 84, Prague, Czech Republic. Electronic address: hana.hromadkova@lfmotol.cuni.cz. FAU - Sumnik, Zdenek AU - Sumnik Z AD - Department of Pediatrics, Charles University, 2nd Faculty of Medicine, University Hospital Motol, V Uvalu 84, Prague, Czech Republic. Electronic address: zdenek.sumnik@lfmotol.cuni.cz. FAU - Kolouskova, Stanislava AU - Kolouskova S AD - Department of Pediatrics, Charles University, 2nd Faculty of Medicine, University Hospital Motol, V Uvalu 84, Prague, Czech Republic. Electronic address: stanislava.kolouskova@lfmotol.cuni.cz. FAU - Spisek, Radek AU - Spisek R AD - Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, V Uvalu 84, Prague, Czech Republic; Sotio a.s., Jankovcova 2, Prague, Czech Republic. Electronic address: spisek@sotio.com. FAU - Sediva, Anna AU - Sediva A AD - Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, V Uvalu 84, Prague, Czech Republic. Electronic address: anna.sediva@fnmotol.cz. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140405 PL - United States TA - Clin Immunol JT - Clinical immunology (Orlando, Fla.) JID - 100883537 RN - 0 (CpG ODN 2216) RN - 0 (Interferon-alpha) RN - 0 (Ligands) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (Toll-Like Receptor 9) SB - IM MH - Adolescent MH - Adult MH - Cell Count MH - Child MH - Child, Preschool MH - Dendritic Cells/*immunology/*metabolism MH - Diabetes Mellitus, Type 1/*immunology/*metabolism MH - Family MH - Female MH - Humans MH - Interferon-alpha/*biosynthesis/blood MH - Leukocytes, Mononuclear/drug effects/metabolism MH - Ligands MH - Male MH - Oligodeoxyribonucleotides/pharmacology MH - Toll-Like Receptor 9/*metabolism MH - Young Adult OTO - NOTNLM OT - Dendritic cell; OT - Interferon-alpha; OT - Type 1 diabetes EDAT- 2014/04/09 06:00 MHDA- 2014/09/13 06:00 CRDT- 2014/04/09 06:00 PHST- 2013/09/27 00:00 [received] PHST- 2014/03/12 00:00 [revised] PHST- 2014/03/26 00:00 [accepted] PHST- 2014/04/09 06:00 [entrez] PHST- 2014/04/09 06:00 [pubmed] PHST- 2014/09/13 06:00 [medline] AID - S1521-6616(14)00082-5 [pii] AID - 10.1016/j.clim.2014.03.018 [doi] PST - ppublish SO - Clin Immunol. 2014 Jul;153(1):49-55. doi: 10.1016/j.clim.2014.03.018. Epub 2014 Apr 5.