Linked Life Data

11120869

Source:http://linkedlifedata.com/resource/pubmed/id/11120869

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2000-12-21
pubmed:abstractText
Neonatal islet-specific expression of IL-10 in nonobese diabetic (NOD) mice accelerates the onset of diabetes, whereas systemic treatment of young NOD mice with IL-10 prevents diabetes. The mechanism for acceleration of diabetes in IL-10-NOD mice is not known. Here we show, by adoptive transfers, that prediabetic or diabetic NOD splenocytes upon encountering IL-10 in the pancreatic islets readily promoted diabetes. This outcome suggests that the compartment of exposure, not the timing, confers proinflammatory effects on this molecule. Moreover, injection of IL-10-deficient NOD splenocytes into transgenic IL-10-NOD.scid/scid mice elicited accelerated disease, demonstrating that pancreatic IL-10 but not endogenous IL-10 is sufficient for the acceleration of diabetes. Immunohistochemical analysis revealed hyperexpression of ICAM-1 on the vascular endothelium of IL-10-NOD mice. The finding suggests that IL-10 may promote diabetes via an ICAM-1-dependent pathway. We found that introduction of ICAM-1 deficiency into IL-10-NOD mice as well as into NOD mice prevented accelerated insulitis and diabetes. Failure to develop insulitis and diabetes was preceded by the absence of GAD65-specific T cell responses. The data suggest that ICAM-1 plays a role in the formation of the "immunological synapse", thereby affecting the generation and/or expansion of islet-specific T cells. In addition, ICAM-1 also played a role in the effector phase of autoimmune diabetes because adoptive transfer of diabetogenic BDC2.5 T cells failed to elicit clinical disease in ICAM-1-deficient IL-10-NOD and NOD mice. These findings provide evidence that pancreatic IL-10 is sufficient to drive pathogenic autoimmune responses and accelerates diabetes via an ICAM-1-dependent pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
165
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7330-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11120869-Adoptive Transfer, pubmed-meshheading:11120869-Animals, pubmed-meshheading:11120869-Autoantigens, pubmed-meshheading:11120869-Diabetes Mellitus, Type 1, pubmed-meshheading:11120869-Female, pubmed-meshheading:11120869-Glutamate Decarboxylase, pubmed-meshheading:11120869-Immunity, Innate, pubmed-meshheading:11120869-Intercellular Adhesion Molecule-1, pubmed-meshheading:11120869-Interleukin-10, pubmed-meshheading:11120869-Islets of Langerhans, pubmed-meshheading:11120869-Isoenzymes, pubmed-meshheading:11120869-Lymphocyte Activation, pubmed-meshheading:11120869-Lymphocyte Transfusion, pubmed-meshheading:11120869-Mice, pubmed-meshheading:11120869-Mice, Inbred BALB C, pubmed-meshheading:11120869-Mice, Inbred NOD, pubmed-meshheading:11120869-Mice, Knockout, pubmed-meshheading:11120869-Mice, SCID, pubmed-meshheading:11120869-Mice, Transgenic, pubmed-meshheading:11120869-Pancreas, pubmed-meshheading:11120869-Spleen, pubmed-meshheading:11120869-T-Lymphocytes, pubmed-meshheading:11120869-Transgenes
pubmed:year
2000
pubmed:articleTitle
A mechanism for IL-10-mediated diabetes in the nonobese diabetic (NOD) mouse: ICAM-1 deficiency blocks accelerated diabetes.
pubmed:affiliation
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't