title: Autoimmune diabetes is blocked in Stat4-deficient mice.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Virginia, P.O. Box 801413, Charlottesville, VA 22908, USA. zy4q@virginia.edu
authors.forename: Zandong
authors.initials: Z
authors.lastname: Yang
authors.forename: Meng
authors.initials: M
authors.lastname: Chen
authors.forename: Justin D
authors.initials: JD
authors.lastname: Ellett
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Fialkow
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Carter
authors.forename: Marcia
authors.initials: M
authors.lastname: McDuffie
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Nadler
mesh_terms: 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
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D007328:Insulin; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators