Regeneration of immune severance system by the repertoire regulation

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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).