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


CONCLUSIONS
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.
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.
Jana
J
Kayserova
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.
Jana
J
Vcelakova
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.
Katerina
K
Stechova
Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, V Uvalu 84, Prague, Czech Republic. Electronic address: eva.dudkova@fnmotol.cz.
Eva
E
Dudkova
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.
Hana
H
Hromadkova
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.
Zdenek
Z
Sumnik
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.
Stanislava
S
Kolouskova
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.
Radek
R
Spisek
Department of Immunology, Charles University, 2nd Faculty of Medicine, University Hospital Motol, V Uvalu 84, Prague, Czech Republic. Electronic address: anna.sediva@fnmotol.cz.
Anna
A
Sediva
D000293:Adolescent; D000328:Adult; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism*; D005190:Family; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D051217:Toll-Like Receptor 9 / Q000378:metabolism* / Q000819:agonists; D055815:Young Adult
C526902:CpG ODN 2216; D016898:Interferon-alpha; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9
Dendritic cell;; Interferon-alpha;; Type 1 diabetes