嗜中性粒细胞是血液中数量最多的免疫细胞，具有重要的免疫作用。我们将通过肌动蛋白聚合极化分析、NADPH 氧化酶激活及颗粒分泌分析和成像流式细胞术等研究方法在Wiskott-Aldrich综合征中研究FRP信号及嗜中性粒细胞的功能，阐明肌动蛋白细胞骨架参与调节FPR信号的分子机制。这将使我们进一步了解WAS蛋白缺陷导致的固有免疫缺陷，可进一步探究肌动蛋白细胞骨架调节FPR信号功能与Wiskott-Aldrich 综合征基因型-表现型的关系。同时这个项目将会创造一个国际化的研究环境，帮助在中国建立相关的研究技术。本研究所得有关肌动蛋白细胞骨架缺陷而造成的免疫缺陷病的研究成果将有助于开启Wiskott-Aldrich综合征临床前沿基因治疗研究，有关FPR活化和脱敏过程的理解将会有助于更有效的开发基于FPR信号的新型药物用于炎症和自身免疫病治疗。

Neutrophils, the most abundant immune cells in the blood, play a key role in host defence and immune regulation. we will investigate the association of the actin cytoskeleton with FPR signaling and neutrophil functions in Wiskott-Aldrich syndrome patients to elucidate the precise molecular mechanism underlying by actin polymerization/polarization assays, chemotaxis, NADPH-oxidase activation granule secretion and receptor-mediated signaling. The research make it possible for us to understand innate immunodeficiency in Wiskott-Aldrich syndrome and whether actin cytoskeleton in regulating receptor signaling and neutrophil activation is associated with the genotype-phenotype.Through this translational research, we will create an international research environment with cutting edge research,and help transfer phagocyte biology and some of the state of the art methods to China. Knowledge obtained from studies of this rare immunodeficiency with defect in the actin cytoskeleton may help to set the stage for preclinical gene therapy studies. In addition,such knowledge on understanding the basis of FPR activation and desensitization should also facilitate more effective FPR-based drug discovery for treating inflammatory and autoimmune diseases.