Induction of Type I Diabetes by Interferon-α in Transgenic Mice

• Published in: Science (American Association for the Advancement of Science) Vol. 260; no. 5116; pp. 1942 - 1946
• Main Authors: Stewart, T. A., Hultgren, B., Huang, X., Pitts-Meek, S., Hully, J., MacLachlan, N. J.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 25-06-1993; American Association for the Advancement of Science
• Subjects: AIDS/HIV; Animals; Antibodies; Antibodies, Monoclonal - therapeutic use; B lymphocytes; Biological and medical sciences; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes; Diabetes; Diabetes complications; Diabetes mellitus; Diabetes Mellitus, Type 1 - etiology; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glucagon - analysis; Insulin; Insulin - analysis; Insulin - blood; Interferon alpha; Interferon-alpha - biosynthesis; Interferon-alpha - immunology; Islet cells; Islets of Langerhans - immunology; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Leukocytes, Mononuclear; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Natural killer cells; Neutralization Tests; Physiological aspects; Somatostatin - analysis; Transgenic animals; Type 1 diabetes mellitus; Endocrinopathy; Immunopathology; Animal model; B-Cell; Alpha interferon; Pathogenesis; Cytokine; Transgenic animal; Insulin dependent diabetes; Autoimmune disease; Pancreas
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8100367

Type I diabetes is an autoimmune disease involving an interaction between an epigenetic event (possibly a viral infection), the pancreatic β cells, and the immune system in a genetically susceptible host. The possibility that the type I interferons could mediate this interaction was tested with transgenic mice in which the insulin-producing β cells expressed an interferon-α. These mice developed a hypoinsulinemic diabetes associated with a mixed inflammation centered on the islets. The inflammation and the diabetes were prevented with a neutralizing antibody to the interferon-α. Thus, the expression of interferon-α by the β cells could be causal in the development of type I diabetes, which suggests a therapeutic approach to this disease.