S1P5是近年来发现的NK细胞非常重要的一个趋化因子受体，调节NK细胞体内分布的稳定及在病变部位的趣化，但对GVHD的影响及作用机制并不清楚。我们的初步结果显示，异基因造血干细胞移植后NK细胞S1P5表达下调易发生GVHD，本课题拟采用基因转染、RNA干涉、动物移植模型、荧光素体内成像系统等以明确S1P5与GVHD、GVT发生之间的关系及其相关机制。研究内容包括：体内、外S1P5表达变化对NK细胞增殖能力、表面表型、细胞因子等生物学特性的影响；体内、外S1P5表达不同的NK细胞对MLR、T细胞、DC细胞的作用与机制；体内NK细胞S1P5表达变化对其体内分布、GVHD、GVT的影响及相关机制。上述研究内容有助于深入阐明GVHD发生的机制，并希望建立GVHD预警或诊断的生物学标志，另外为平衡GVHD和GVT作用提供实验数据。通过该项研究还为下一步探索治疗靶点，开发新的药物打下基础。

Recently reported,S1P5 is very important chemokine receptor of NK cells that governs NK cell trafficking in steady-state situation and rapid mobilization in inflammatory conditions.The effect and mechanism of S1P5 on GVHD are unclear.Our preliminary results show that S1P5 expression downregulation of NK cells can cause occurrence of GVHD after allogeneice hematopoietic stem cell transplantation.In this project,to define relationship of S1P5 and GVHD or GVT,we intend to use gene transfer,RNA interference,animal transplant model, fluorescence imaging system for living animal and so on.The study includes the influence of S1P5 expression changes on proliferative capacity,phenotype,cytokines and other biological characteristics of NK cells in vivo and vitro;the effect and mechanism of NK cells with different S1P5 expression on mixed lymphocyte reaction (MLR),T cells and dendritic cells (DC) in vivo and vitro; the effect and mechanism S1P5 exprassion changes on NK cell trafficking,GVHD and GVT in vivo.The above studies contribute to further elucidating the mechanism of GVHD,hope to establish biological markers for GVHD warning or diagnosis,pvovide experimental data to balance GVHD and GVT,and also lay the fundation for the next step to explore therapeutic targets and development of new drugs.