| First Author | Martin S | Year | 2001 |
| Journal | J Autoimmun | Volume | 17 |
| Issue | 2 | Pages | 109-17 |
| PubMed ID | 11591119 | Mgi Jnum | J:71827 |
| Mgi Id | MGI:2150855 | Doi | 10.1006/jaut.2001.0526 |
| Citation | Martin S, et al. (2001) Dominant role of intercellular adhesion molecule-1 in the pathogenesis of autoimmune diabetes in non-obese diabetic mice. J Autoimmun 17(2):109-17 |
| abstractText | 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% of ICAM-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-gamma, interleukin (IL)-12p40 and IL-12p35 pancreatic mRNA levels, leading to an increased ratio of IFN-gamma: IL-4 and IL-12p40: IL-12p35 expression. In contrast, ICAM-1(-/-)NOD mice did not upregulate IFN-gamma 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. |
