Development of strategy to treat immune and allergic diseases targeting molecules associated with NF-kB activation

我们对两种缺乏TRAF 2或c-FLIP的缺陷小鼠进行了表征，这两种缺陷小鼠都在保护细胞免受TNFα诱导的凋亡中发挥重要作用。TRAF 2缺陷小鼠通过增强结肠上皮细胞凋亡和随后的肠道微生物群改变和促炎细胞因子上调自发发展为重度肝炎。为了删除c-Flip基因，我们将poly I：C注射到干扰素诱导的c-FlipF/F：Mx缺陷小鼠中。注射poly I：C后，c-FlipF/F：Mx小鼠发生了重度肝炎，沿着IL-6上调，但TNFα或IL-1β未上调。总的来说，这些结果表明，与TNFα信号相关的衔接分子的缺失促进细胞凋亡沿着炎症。

We characterized two deficient mice lacking TRAF2 or c-FLIP, both of which are critically involved in protection of cells from TNFα-induced apoptosis. TRAF2-deficient mice spontaneously developed severe hepatitis through enhanced apoptosis of the colonic epithelial cells and subsequent alterations of the commensal microbiota and upregulation of proinflammatory cytokines. To delete c-Flip gene, we injected poly I:C into interferon-inducible c-Flip-deficient (c-FlipF/F:Mx) mice. Upon poly I:C injection, c-FlipF/F:Mx mice developed severe hepatitis along with upregulation of IL-6, but not TNFα or IL-1β. Collectively, these results suggest that deletion of adaptor molecules associated with TNFα signalings promotes apoptosis along with inflammation.