Development of new therapy for type 1 diabetes targeting for IRF-4 (interferon regulatory factor-4)

点击翻译按钮获取中文摘要

To investigate the effectiveness of IRF4 targeting therapy in type 1 diabetes, we generated IRF4 deficient NOD mouse and investigated the phenotypes. We found that progression of autoimmune diabetes / insulitis / autoinsulin antibody were completely suppressed in IRF4-/- NOD mice, also significantly suppressed in heterozygous (IRF4+/-NOD) mice. Adaptive transfer study with combined CD4+and CD8+T cell subsets exhibited that IRF4 is essential for effecter functions in both CD4+ and CD8+ T cells. Less IRF4 expression was associated with reduction of memory T cells and IL-17 producing CD4+T cells, as well as Granzym B producing cells in CD8+T cells. We documented IRF4 is essential for effector function of T cells in autoimmune diabetes in NOD mouse and IRF4 is possible target for prevention for human type 1 diabetes