Complete suppression of insulitis and diabetes in NOD mice lacking interferon regulatory factor-1

Tetsuya Nakazawa, Jo Satoh, Kazuma Takahashi, Yoshiyuki Sakata, Fumiko Ikehata, Yumiko Takizawa, Shin Ichiro Bando, Toshimune Housai, Yan Li, Chen Chen, Takayuki Masuda, Shigeo Kure, Ichiro Kato, Shin Takasawa, Tadatsugu Taniguchi, Hiroshi Okamoto, Takayoshi Toyota

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58 Citations (Scopus)


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 β-cell, significantly increased, and the IFN-γ/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.

Original languageEnglish
Pages (from-to)119-125
Number of pages7
JournalJournal of Autoimmunity
Issue number2
Publication statusPublished - 2001 Sept 1


  • IRF-1
  • NOD mice
  • Th1 and Th2 cytokine
  • Type 1 diabetes mellitus


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