Analysis of in vivo role of STAT3

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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.