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

为了研究IRF4靶向治疗1型糖尿病的有效性，我们建立了IRF4基因缺陷的NOD小鼠，并对其表型进行了研究。我们发现，在IRF4+/-NOD小鼠中，自身免疫性糖尿病/胰岛素炎/自身胰岛素抗体的进展完全受到抑制，在杂合子(IRF4+/-NOD)小鼠中也显著受到抑制。结合CD4+和CD8+T细胞亚群的适应性转移研究表明，IRF4对CD4+和CD8+T细胞的效应功能都是必不可少的。IRF4表达减少与CD8+T细胞中产生Granzym B的T细胞和产生IL-17的CD4+T细胞减少有关。我们证明IRF4在NOD小鼠自身免疫性糖尿病中对T细胞的效应功能是必不可少的，并且IRF4可能是预防人类1型糖尿病的靶点

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