Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Haploinsufficiency of Interferon regulatory factor 4 strongly protects from autoimmune diabetes in the non-obese diabetic mice (#137)

Satoru Akazawa 1 , Masakazu Kobayashi 1 , Eiji Kawasaki 2 , Yuji Nagayama 3 , Katsuyuki Yui 4 , Toshifumi Matsuyama 5 , Atsushi Kawakami 1 , Norio Abiru 1
  1. Department of Endocrinology and Metabolism, Unit of Translational Medicine, Nagasaki University Hospital, Nagasaki, Japan
  2. Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital, Nagasaki, Japan
  3. Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  4. Division of Immunology, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  5. Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japna

Genetic deletion of interferon regulatory factor 4 (IRF4), a member of the IRF family of transcriptional factors, has been shown to protect from autoimmune disease in several mouse models but not in non-obese diabetic (NOD) mouse. We have developed IRF4 deficient NOD mice and found that diabetes/insulitis and autoantibody production were completely suppressed in IRF4-deficient heterozygous as well as homozygous NOD mice. Adoptive transfer study into NOD-Scid mice showed that total deficiency of IRF4 or alternate deficiency in either CD4+, CD8+ T cells from the transferred effector T cells protected from diabetes although heterozygous deficiency of IRF-4 conferred partial disease resistance. Homozygous, but not heterozygous IRF4 deficiency diminished the number of memory, naïve or IL-17 producing cells in CD4+ T cells and granzyme B /perforine producing cells in CD8+ T cells.
These results indicated that an expression of IRF4 in both CD4+ and CD8+ T cells plays a critical role in developing autoimmune diabetes and that haploinsufficiency of IRF4 protects from diabetes in the NOD mice.