Source:http://linkedlifedata.com/resource/pubmed/id/20639483
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2010-8-5
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| pubmed:abstractText |
Development of type 1 diabetes (T1D) is preceded by invasive insulitis. Although CD4(+)CD25(+) regulatory T cells (nTregs) induce tolerance that inhibits insulitis and T1D, the in vivo cellular mechanisms underlying this process remain largely unclear. Using an adoptive transfer model and noninvasive imaging-guided longitudinal analyses, we found nTreg depletion did not affect systemic trafficking and tissue localization of diabetogenic CD4(+) BDC2.5 T (BDC) cells in recipient mice prior to development of T1D. In addition, neither the initial expansion/activation of BDC cells nor the number of CD11c(+) or NK cells in islets and pancreatic lymph nodes were altered. Unexpectedly, our results showed nTreg depletion led to accelerated invasive insulitis dominated by CD11c(+) dendritic cells (ISL-DCs), not BDC cells, which stayed in the islet periphery. Compared with control mice, the phenotype of ISL-DCs and their ability to stimulate BDC cells did not change during invasive insulitis development. However, ISL-DCs from nTreg-deficient recipient mice showed increased in vitro migration toward CCL19 and CCL21. These results demonstrated invasive insulitis dominated by DCs, not CD4(+) T cells, preceded T1D onset in the absence of nTregs, and suggested a novel in vivo function of nTregs in T1D prevention by regulating local invasiveness of DCs into islets, at least partly, through regulation of DC chemotaxis toward CCL19/CCL21 produced by the islets.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
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| pubmed:issn |
1550-6606
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
185
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2493-501
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| pubmed:meshHeading |
pubmed-meshheading:20639483-Adoptive Transfer,
pubmed-meshheading:20639483-Animals,
pubmed-meshheading:20639483-Antigens, CD11c,
pubmed-meshheading:20639483-Cell Movement,
pubmed-meshheading:20639483-Chemokine CCL19,
pubmed-meshheading:20639483-Chemokine CCL21,
pubmed-meshheading:20639483-Chemotaxis,
pubmed-meshheading:20639483-Dendritic Cells,
pubmed-meshheading:20639483-Diabetes Mellitus, Type 1,
pubmed-meshheading:20639483-Flow Cytometry,
pubmed-meshheading:20639483-Inflammation,
pubmed-meshheading:20639483-Interleukin-2 Receptor alpha Subunit,
pubmed-meshheading:20639483-Islets of Langerhans,
pubmed-meshheading:20639483-Killer Cells, Natural,
pubmed-meshheading:20639483-Mice,
pubmed-meshheading:20639483-Mice, Inbred NOD,
pubmed-meshheading:20639483-Mice, Transgenic,
pubmed-meshheading:20639483-Prediabetic State,
pubmed-meshheading:20639483-T-Lymphocytes,
pubmed-meshheading:20639483-T-Lymphocytes, Regulatory,
pubmed-meshheading:20639483-Time Factors
|
| pubmed:year |
2010
|
| pubmed:articleTitle |
CD4+ CD25+ regulatory T cells prevent type 1 diabetes preceded by dendritic cell-dominant invasive insulitis by affecting chemotaxis and local invasiveness of dendritic cells.
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| pubmed:affiliation |
Department of Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|