| Altered Toll-like receptor signaling pathways in human type 1 diabetes. | |
| | |
MedLine Citation:
|
PMID: 20725710 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
There is compelling evidence from animal models of type 1 diabetes (T1D) that the innate immune system plays a key role in early mechanisms triggering islet destruction. Very little is known, however, about innate immune subsets and pathways potentially involved in mechanisms leading to human T1D. The present study used a comprehensive approach to analyze innate immune functions in primary monocytes and dendritic cells (DCs) from newly diagnosed patients with T1D versus age-matched healthy individuals. We observed that incubation of PBMCs in the presence of the TLR7/8 agonist R848 led to increased proportion of plasmacytoid dendritic cells (pDCs) expressing IFN-α in patients versus healthy control subjects. We also found that TLR4 activation induced a higher frequency of IL-1β expressing monocytes and a reduction in the percentage of IL-6 expressing myeloid dendritic cells (mDCs). The altered TLR responsiveness was not due to aberrant proportions of peripheral DC subsets and monocytes in the blood and did not correlate with altered hemoglobin A1c and the expression of diabetes susceptibility genes but could potentially be associated with enhanced nuclear factor-kappa B signaling. Finally, we observed that levels of serum IFN-α2, IL-1β, IFN-γ, and CXCL-10 were elevated in new onset patients versus the control group. Taken together, our observations provide evidence that altered innate immunity exists in mDCs and pDCs from T1D and raise the possibility that these alterations may be associated with disease mechanisms. |
| | |
Authors:
|
Adam J Meyers; Roopali R Shah; Peter A Gottlieb; Danny Zipris |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-20 |
Journal Detail:
|
Title: Journal of molecular medicine (Berlin, Germany) Volume: 88 ISSN: 1432-1440 ISO Abbreviation: J. Mol. Med. Publication Date: 2010 Dec |
Date Detail:
|
Created Date: 2010-11-16 Completed Date: 2011-04-04 Revised Date: 2011-07-08 |
Medline Journal Info:
|
Nlm Unique ID: 9504370 Medline TA: J Mol Med (Berl) Country: Germany |
Other Details:
|
Languages: eng Pagination: 1221-31 Citation Subset: IM |
Affiliation:
|
Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, 1775 Aurora Ct., Mail Stop B-140, Aurora, CO 80045, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adolescent Adult Case-Control Studies Chemokines / blood Child Child, Preschool Dendritic Cells / immunology Diabetes Mellitus, Type 1 / blood, diagnosis, immunology* Female Humans Inflammation Mediators / metabolism Male Monocytes / immunology NF-kappa B / metabolism Phosphorylation Signal Transduction / immunology* Toll-Like Receptors / immunology* Up-Regulation Young Adult |
| Chemical | |
Reg. No./Substance:
|
0/Chemokines; 0/Inflammation Mediators; 0/NF-kappa B; 0/Toll-Like Receptors |
| Comments/Corrections | |
Comment In:
|
J Mol Med (Berl). 2010 Dec;88(12):1191-4
[PMID:
21080152
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: [Congenital thrombocytopathies].
Next Document: Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease.