禽流感病毒（AIV）一般在鸟类间传播，但H5N1等高致病性AIV可跨物种感染人类。高致病性AIV诱发宿主急性肺损伤（ALI）是其高致死率的主要原因。ALI主要由免疫系统过度激活引起的“细胞因子风暴”导致，但AIV激活免疫系统的机制尚不完全明确。前期研究发现，细胞表面CD83介导AIV激活TLR4信号通路，活化免疫细胞调控细胞因子表达释放，诱导CD4+T细胞Th17分化。本项目拟在前期研究基础上，分析细胞表面CD83与MD-2/TLR4复合体的结合形式，观察CD83对AIV激活TLR4下游信号通路的影响，明确CD83在AIV激活DC诱导CD4+T细胞Th17分化过程中的作用，检验重组CD83对AIV诱发ALI的抑制作用。本课题的设计与实施不仅可以阐明细胞表面CD83在AIV感染致ALI过程中的作用机制，还能够验证重组CD83在AIV感染中发挥的治疗作用，有望为禽流感的防治提供新思路及新靶点。

Avian influenza virus (AIV) is generally transmitted among birds, but highly pathogenic AIVs such as H5N1 can infect humans across species. Acute lung injury (ALI) induced by highly pathogenic AIV is the main reason for its high mortality. "Cytokine storm" leads to excessive activation of the immune system is the main cause of ALI, but the mechanism remains unclear. Ours previous studies found that membrane CD83 participated in the AIV-induced activation of TLR4 signaling pathway, resulting in the activity of immune cells to regulate cytokine expression and release, as well as CD4 + T cell Th17 polarization. Base on previous research, this project is intended to analyze the binding form of membrane CD83 and MD-2 / TLR4 complex, observe the effect of CD83 on AIV-activated TLR4 downstream signaling pathways, and clarify the role of CD83 on AIV-activated DCs to induce CD4+T cells Th17 polarization, further verify the inhibitory effect of recombinant CD83 on AIV-induced ALI. The design and implementation of this project can not only clarify the mechanism of membrane CD83 in AIV-induced ALI infection, but also verify the therapeutic function of recombinant CD83 in AIV infection. The finding will have great potential to contribute to development of new treatment strategies for avian influenza.