Autoimmune diabetes is blocked in Stat4-deficient mice.
Signal transducers and activators of transcription (STAT) proteins are activated in response to many cytokines, growth factors and hormones. STAT4 mediates IL-12 signaling and regulates T helper 1 (Th1) cell differentiation. Both IL-12 and Th1 cell activation participate in the development of autoimmune diabetes. In this study, we investigated the role of STAT4 in autoimmune diabetes. We crossbred Stat4 deficient (Stat4-/-) mice with nonobese diabetic (NOD) mice to generate the Stat4-/- NOD model. In Stat4-/- NOD mice, serum levels of both IFN-gamma and IL-2 were significantly reduced as compared to the controls. Insulin secretion in pancreatic islets was preserved in Stat4-/- NOD mice. Significantly, disruption of Stat4 activation completely prevented the development of spontaneous diabetes in NOD mice. This study reveals the important role of STAT4 in autoimmune diabetes pathogenesis.
Yang
Zandong
Z
Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Virginia, P.O. Box 801413, Charlottesville, VA 22908, USA. zy4q@virginia.edu
Chen
Meng
M
Ellett
Justin D
JD
Fialkow
Lawrence B
LB
Carter
Jeffrey D
JD
McDuffie
Marcia
M
Nadler
Jerry L
JL
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D020297:Mice, Congenic; D016688:Mice, Inbred NOD; D050797:STAT4 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics* / Q000276:immunology
D016207:Cytokines; D004268:DNA-Binding Proteins; D007328:Insulin; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators