RGD Reference Report - Disruption of the STAT4 signaling pathway protects from autoimmune diabetes while retaining antiviral immune competence. - Rat Genome Database

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Disruption of the STAT4 signaling pathway protects from autoimmune diabetes while retaining antiviral immune competence.

Authors: Holz, A  Bot, A  Coon, B  Wolfe, T  Grusby, MJ  Von Herrath, MG 
Citation: Holz A, etal., J Immunol. 1999 Nov 15;163(10):5374-82.
RGD ID: 7207889
Pubmed: PMID:10553062   (View Abstract at PubMed)

The role of the STAT4 signaling pathway in autoimmune diabetes was investigated using the rat insulin promoter lymphocytic choriomeningitis virus model of virally induced autoimmune diabetes. Abrogation of STAT4 signaling significantly reduced the development of CD4+-T cell-dependent but not CD4+-T cell-independent diabetes, illustrating the fine-tuned kinetics involved in the pathogenesis of autoimmunity. However, the absence of STAT4 did not prevent the generation of autoreactive Th1/Tc1 T cell responses, as well as protective antiviral immunity. Protection from insulin-dependent diabetes mellitus was associated with decreased numbers of autoreactive CTL precursors in the pancreas and the spleen and a general as well as Ag-specific reduction of IFN-gamma secretion by T lymphocytes. A shift from Th1 to Th2 T cell immunity was not observed. Hence, our results implicate both CTL and cytokines in beta cell destruction. Selective inhibition of the STAT4 signal transduction pathway might constitute a novel and attractive approach to prevent clinical insulin-dependent diabetes mellitus in prediabetic individuals at risk.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOStat4 (Mus musculus)7207889; 7207889 RGD 
Experimental Diabetes Mellitus  IMP 7207889 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Stat4  (signal transducer and activator of transcription 4)

Genes (Mus musculus)
Stat4  (signal transducer and activator of transcription 4)

Genes (Homo sapiens)
STAT4  (signal transducer and activator of transcription 4)


Additional Information