Decreased dendritic cell numbers but increased TLR9-mediated interferon-alpha production in first degree relatives of type 1 diabetes patients
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24709112
DOI
10.1016/j.clim.2014.03.018
PII: S1521-6616(14)00082-5
Knihovny.cz E-resources
- Keywords
- Dendritic cell;, Interferon-alpha;, Type 1 diabetes,
- MeSH
- Dendritic Cells immunology metabolism MeSH
- Diabetes Mellitus, Type 1 immunology metabolism MeSH
- Child MeSH
- Adult MeSH
- Interferon-alpha biosynthesis blood MeSH
- Leukocytes, Mononuclear drug effects metabolism MeSH
- Humans MeSH
- Ligands MeSH
- Adolescent MeSH
- Young Adult MeSH
- Oligodeoxyribonucleotides pharmacology MeSH
- Cell Count MeSH
- Child, Preschool MeSH
- Family MeSH
- Toll-Like Receptor 9 metabolism MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- CpG ODN 2216 MeSH Browser
- Interferon-alpha MeSH
- Ligands MeSH
- Oligodeoxyribonucleotides MeSH
- Toll-Like Receptor 9 MeSH
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.
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