| First Author | Nakazawa T | Year | 2001 |
| Journal | J Autoimmun | Volume | 17 |
| Issue | 2 | Pages | 119-25 |
| PubMed ID | 11591120 | Mgi Jnum | J:71799 |
| Mgi Id | MGI:2150815 | Doi | 10.1006/jaut.2001.0531 |
| Citation | Nakazawa T, et al. (2001) Complete Suppression of Insulitis and Diabetes in NOD mice Lacking Interferon Regulatory Factor-1. J Autoimmun 17(2):119-25 |
| abstractText | Interferon regulatory factor-1 (IRF-1), a transcriptional factor, regulates type I interferon and interferon-induced genes. It was reported that IRF-1 regulates important molecules required for inflammation and immune reactions. To investigate the role of IRF-1 in the development of autoimmune diabetes, we established IRF-1 deficient (IRF-1(-/-)) non-obese diabetic (NOD) mice. IRF-1-deficient C57BL/6J mice were out-crossed to NOD mice, and F1 were backcrossed to NOD mice. At the N8 generation, the heterozygote for IRF-1 mutation was intercrossed and N8F1 was obtained. Out of three NOD genotypes, IRF-1(+/+)and IRF-1(+/-)developed spontaneous diabetes with an incidence of 47% (9/19) and 50% (10/20) by 30 weeks of age, respectively; whereas IRF-1(-/-)did not develop diabetes (0/18, P< 0.01 vs.(+/+)and(+/-)). Histologically, IRF-1(+/+)and IRF-1(+/-)had various degrees of insulitis, but IRF-1(-/-)had no insulitis. In comparison with IRF-1(+/+), the percentage of CD4(+)and Mac-1(+)splenic cells significantly increased, whereas CD3(+), CD8(+)and B220(+)cells decreased in IRF-1(-/-). Furthermore, spleen cell proliferation in response to Con A or murine GAD65 peptide, a major autoantigen of the pancreatic beta-cell, significantly increased, and the IFN-gamma/IL-10 ratio in the culture supernatant significantly decreased in IRF-1(-/-), suggesting Th2 deviation in cytokine balance. These results indicate that IRF-1 plays a key role in developing insulitis and diabetes in NOD mice. |
