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Regeneration of immune severance system by the repertoire regulation

通过库调节实现免疫切断系统的再生

基本信息

批准号：
15078102
负责人：
KUBO Masato
金额：
$ 78.08万
依托单位：
RIKEN (2004-2006)Tokyo University of Science (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15078102/
关键词：
Cytokine Suppression Signal septic peritonitis liver injury T cell メモリーT細胞 T細胞機能分化サイトカインバランス Th1 Th2 免疫監視 IL-4 SOCS

项目摘要

Cytokine regulate the survival, proliferation, differentiation and function of immune cells as well as cells from most other organ systems. Many of these cytokines induce the expression of SOCS proteins, a feedback inhibitor of JAK kinase. It still remains unclear how cytokine signaling regulates immune homeostasis. In this year, we studied a role of SOCS5 in septic peritonitis, and demonstrate that overexpression of SOCS5 in T cells augments innate immunity during septic peritonitis induced by cecal ligation and puncture (CLP). We also studied the role of SOCS proteins in acetaminophen (APAP)-induced acute liver injury. We demonstrate that forced expression of SOCS3 in T cells exacerbates APAP-hepatotoxicity, indicating that novel sight of SOCS3 function in innate immunity. In order to study naive and memory T cell development in the attenuated cytokine signaling, we generated the T cell specific SOCS1 transgenic lines (SOCS1Tg), and we demonstrated that the cytokine signalings was essential for survival of naive CD4 T cells in the periphery. These data demonstrated that SOCS proteins are key physiological regulators of both innate and adaptive immunity. These molecules positively and negatively regulate macrophage and dendritic-cell activation and are essential for T-cell development and differentiation. We recently reviewed these studies on SOCS proteins and their role in immunity (Nature Review Immunology).

细胞因子调节免疫细胞以及来自大多数其他器官系统的细胞的存活、增殖、分化和功能。这些细胞因子中的许多诱导SOCS蛋白的表达，SOCS蛋白是JAK激酶的反馈抑制剂。目前尚不清楚细胞因子信号如何调节免疫稳态。今年，我们研究了SOCS5在脓毒性腹膜炎中的作用，并证明了T细胞中SOCS5的过表达在盲肠结扎和穿孔（CLP）诱导的脓毒性腹膜炎期间增强了先天免疫。我们还研究了SOCS蛋白在对乙酰氨基酚（APAP）诱导的急性肝损伤中的作用。我们证明了SOCS3在T细胞中的强制表达加剧了APAP肝毒性，表明SOCS3在先天免疫中的功能的新观点。为了研究在减弱的细胞因子信号传导中幼稚和记忆T细胞的发育，我们产生了T细胞特异性SOCS1转基因系（SOCS1Tg），并且我们证明了细胞因子信号传导对于幼稚CD4 T细胞在外周中的存活是必需的。这些数据表明，SOCS蛋白是先天免疫和适应性免疫的关键生理调节剂。这些分子积极和消极地调节巨噬细胞和树突状细胞的活化，是T细胞发育和分化所必需的。我们最近回顾了这些关于SOCS蛋白及其在免疫中的作用的研究（Nature Review Immunology）。