Regeneration of immune severance system by the repertoire regulation

细胞因子调节免疫细胞以及大多数其他器官系统细胞的存活、增殖、分化和功能。许多这些细胞因子诱导SOCS蛋白的表达，SOCS蛋白是JAK激酶的一种反馈抑制剂。细胞因子信号如何调节免疫稳态仍不清楚。本年度，我们研究了SOCS5在脓毒性腹膜炎中的作用，并证明在盲肠结扎穿刺（CLP）引起的脓毒性腹膜炎中，T细胞中SOCS5的过表达增强了先天免疫。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，在T细胞中强制表达SOCS3会加剧apap -肝毒性，这表明SOCS3在先天免疫中的功能有了新的认识。为了研究初始T细胞和记忆T细胞在细胞因子信号减弱的情况下的发育，我们产生了T细胞特异性SOCS1转基因系（SOCS1Tg），并证明细胞因子信号对外周血初始CD4 T细胞的存活至关重要。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因子。这些分子正或负调节巨噬细胞和树突状细胞的活化，对t细胞的发育和分化至关重要。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）。

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).