Dominant Role of Intercellular Adhesion Molecule-1 in the Pathogenesis of Autoimmune Diabetes in Non-obese Diabetic Mice

• Published in: Journal of autoimmunity 2001-09, Vol.17 (2), p.109-117
• Main Authors: Martin, Stephan, van Den Engel, Natasja K, Vinke, Antje, Heidenthal, Edmund, Schulte, Bettina, Kolb, Hubert
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Crosses, Genetic; Diabetes Mellitus, Type 1 - etiology; Diabetes Mellitus, Type 1 - prevention & control; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; g-Interferon; ICAM-1, knockout, NOD mice, Th1/Th2, type 1 diabetes; Inflammation - immunology; Inflammation - prevention & control; intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - physiology; Islets of Langerhans - immunology; Islets of Langerhans - pathology; Medical sciences; Mice; Mice, Inbred NOD; Mice, Knockout; T-Lymphocyte Subsets - immunology; Th1 Cells - immunology; Th2 Cells - immunology
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.2001.0526

Intercellular adhesion molecule (ICAM)-1 is involved in forming the immunological synapse. The contribution of ICAM-1 to immune responses is not critical because mice with a disrupted ICAM-1 gene do not have grossly abnormal immune reactivity. Here we report on the surprising finding that diabetes-prone NOD mice with a disrupted ICAM-1 gene (ICAM-1−/−) are completely protected from disease development. While 64% ofICAM-1+/+ and 44% of ICAM-1+/−female NOD mice developed overt diabetes until 310 days old, no ICAM-1−/−NOD mice became hyperglycaemic. Histological examinations revealed minor infiltration around pancreatic islets of ICAM1−/−NOD mice. Administration of cyclophosphamide caused a progression to severe islet destruction in ICAM-1+/+NOD mice within 10 days. In contrast, ICAM-1−/−mice showed only mild insulitis. Furthermore,ICAM-1+/+ NOD mice showed an increase of IFN-γ, interleukin (IL)-12p40 and IL-12p35 pancreatic mRNA levels, leading to an increased ratio of IFN-γ: IL-4 and IL-12p40: IL-12p35 expression. In contrast,ICAM-1−/− NOD mice did not upregulate IFN-γ or IL-12p40 gene expression but maintained IL-4 and increased IL-12p35 gene expression. These results identify a dominant and non-redundant role of ICAM-1 in the development of autoimmune diabetes.