诱导型一氧化氮合酶（iNOS）所合成的一氧化氮（NO）在免疫调节中发挥重要作用，iNOS/NO可影响多种免疫细胞的分化和功能，参与调控适应性免疫应答。浆细胞样树突状细胞（pDC）在免疫调控以及免疫相关性疾病发病中发挥至关重要的作用，但iNOS对pDC分化及其功能的影响尚未见报道。我们前期实验证实，pDC来源的iNOS/NO能够抑制pDC的分化成熟，但其调控机制和在感染及炎症性疾病中的作用机制尚不清楚。本课题拟利用iNOS缺陷小鼠，在体外及感染和炎症性疾病模型中深入研究pDC来源的iNOS/NO对pDC的分化和功能的调控作用及机制；分析iNOS对pDC介导的T细胞活化和增殖的影响；明确pDC来源的iNOS通过调控NF-κB和MAPK途径影响pDC分化和成熟的作用机制。本研究将首次阐明iNOS/NO与pDC分化的关系，为自身免疫性疾病和炎症性疾病提供新的治疗策略。

Inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) plays critical roles in the regulation of immune responses. NO also regulates the differentiation, death and function of various immune cells including plasmacytoid dendritic cells (pDC). Howerver, the function of pDC-derived iNOS is still unknown, especially its function in immune response，tolerance in inflammatory diseases and the potential mechanisms. In the present study, we demonstrated that pDC-derived iNOS regulated the differentiation and maturation of pDC. The current proposal will address the hypothesis that iNOS produced by pDC regulates the differentiation and function of pDC with in vitro bone marrow-derived pDC (BM-pDC) and in vivo mouse model of bacteria infection. In addition, we will study the role of iNOS in pDC on T cell activation and proliferation. Finally, we will characterize the significance of pDC-derived iNOS in the control of pDC development and maturation. The proposed studies will provide important clues for the development of new therapies for autoimmune/inflammatory diseases by targeting pDC-derived iNOS.