RGD Reference Report - Local activation of dendritic cells leads to insulitis and development of insulin-dependent diabetes in transgenic mice expressing CD154 on the pancreatic beta-cells. - Rat Genome Database

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Local activation of dendritic cells leads to insulitis and development of insulin-dependent diabetes in transgenic mice expressing CD154 on the pancreatic beta-cells.

Authors: Haase, C  Skak, K  Michelsen, BK  Markholst, H 
Citation: Haase C, etal., Diabetes. 2004 Oct;53(10):2588-95.
RGD ID: 2314220
Pubmed: PMID:15448088   (View Abstract at PubMed)

The initial events leading to activation of the immune system in type 1 diabetes are still largely unknown. In vivo, dendritic cells (DCs) are thought to be the only antigen-presenting cells (APCs) capable of activating naive T-cells and are therefore important for the initiation of the autoimmune response. To test the effect of activating islet-associated APCs in situ, we generated transgenic mice expressing CD154 (CD40 ligand) under control of the rat insulin promoter (RIP). RIP-CD154 mice developed both insulitis and diabetes, although with different incidence in independent lines. We show that activated DCs could be detected both in the pancreas and in the draining pancreatic lymph nodes. Furthermore, diabetes development was dependent on the presence of T- and B-cells since recombination-activating gene (RAG)-deficient RIP-CD154 mice did not develop diabetes. Finally, we show that the activation of immune cells was confined to the pancreas because transplantation of nontransgenic islets to diabetic recipients restored normoglycemia. Together, these data suggest that expression of CD154 on the beta-cells can lead to activation of islet-associated APCs that will travel to the lymph nodes and activate the immune system, leading to insulitis and diabetes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 1 diabetes mellitus  ISOCd40lg (Mus musculus)2314220; 2314220 RGD 
type 1 diabetes mellitus  IMP 2314220 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd40lg  (CD40 ligand)

Genes (Mus musculus)
Cd40lg  (CD40 ligand)

Genes (Homo sapiens)
CD40LG  (CD40 ligand)


Additional Information