清道夫受体SCARB2调节浆样树突状细胞发育和功能的分子机制

浆样树突状细胞(pDC)又被称为干扰素产生细胞，因为pDC在病毒感染或其它刺激下能够产生大量的I型干扰素(IFN-I)。我们已经证明，清道夫受体SCARB2特异性地表达在人pDC并定位于晚期内吞体(late endosome)膜上。SCARB2通过控制TLR9从内质网到晚期内吞体的转运来调节IFN-I的产生(J Immunol，2015)。在此基础之上，我们最近通过CRISPR/Cas9技术获得了SCARB2基因敲除的293T细胞系和SCARB2基因敲除的小鼠。在本项目中，我们将继续深入研究SCARB2影响TLR9转运和IFN-I产生的分子机制。我们还将利用人源化小鼠模型，研究SCARB2对人pDC在体内发育的影响。本研究有利于增进我们对pDC发育和功能的深入了解，为将来开发针对于该细胞或I型干扰素的临床免疫治疗提供理论依据。

Plasmacytoid dendritic cells (pDCs) are also known as interferon producing cells，since they produce large amount of type I interferon (IFN-I) upon viral infection or other stimulations. We have shown that scavenger receptor SCARB2 preferentially expresses in the late endosome of human pDCs and regulates their IFN-I production through controlling the endosomal trafficking of TLR9 from ER (J Immunol, 2015). In addition, we already generated SCARB2 knockout mice and SCARB2 knockout 293T cell line by CRISPR/Cas9 technology. In this project, we propose to further investigate the mechanisms of SCARB2 in regulating TLR9 translocation and IFN-I production by pDCs. Furthermore, we will examine the roles of SCARB2 in the development of human pDCs in humanized mice. This study will advance our understanding of pDC biology and facilitate the development of pDCs or IFN-I based immunotherapies.