Analysis of in vivo role of STAT3

STAT家族蛋白参与细胞因子信号通路。我分析了STAT3在体内的作用。stat3缺陷小鼠是早期胚胎致死的。因此，为了评估STAT3在细胞因子介导的生物学功能中的作用，我们使用Cre-loxP重组系统以组织特异性的方式删除STAT3。首先，我们删除了T细胞中的STAT3。由于缺乏il -6诱导的细胞凋亡预防，stat3缺陷T细胞凋亡增强。当我们删除巨噬细胞中的STAT3时，这些突变小鼠发生慢性小肠结肠炎。由于缺乏il -10介导的巨噬细胞活性抑制，stat3缺陷的巨噬细胞被异常激活。除免疫系统外，我们还删除了乳腺和皮肤中的STAT3。在乳腺中，STAT3已被证明在断奶后诱导上皮细胞凋亡中起重要作用。在皮肤中，STAT3已被证明对生长因子诱导的角质细胞运动增强介导的伤口愈合很重要。因此，STAT3的组织特异性靶向揭示了其在生物学功能的各个方面的重要作用。

STAT family proteins are involved in cytokine signaling pathways. I analyzed in vivo roles of STAT3. STAT3-deficient mice are early embryonic lethal. Therefore, to assess the role of STAT3 in cytokine-mediated biologic functions, we deleted STAT3 in a tissue-specific manner using Cre-loxP recombination system. First, we deleted STAT3 in T cells. STAT3-deficient T cells showed the enhanced apoptosis due to lack of IL-6-induced prevention of apoptosis. When we deleted STAT3 in macrophages, these mutant mice developed chronic enterocolitis. STAT3-deficient macrophages are abnormally activated due to lack of IL-10-mediated suppression of macrophage activity. In addition to the immune system, we deleted STAT3 in mammary gland and skin. In mammary gland, STAT3 has been demonstrated to be important for induction of apoptosis of epithelial cells after weaning. In skin, STAT3 has been shown to be important for wound healing mediated by enhancement of keratinocyte motility induced by growth factors.Thus, tissue-specific targeting of STAT3 revealed its important roles in various aspects of biological functions.