Anti-Inflammatory Polarization of Microglia by ITIM-SHP1 Signalling

小胶质细胞可以被极化成促炎症或抗炎的表型，导致神经元损伤或大脑修复。最近的数据表明，免疫受体酪氨酸抑制基序(ITIM)-SHP1酪氨酸磷酸酶信号转导通路有助于小胶质细胞的抗炎表型。在本项目中，我们将使用来自小鼠胚胎和人类诱导的多能干细胞的小胶质细胞以及条件性SHP1基因敲除小鼠来研究ITIM-SHP1在小胶质细胞中的功能。此外，人类免疫受体CD33在小胶质细胞ITIM-SHP1信号传递中的作用将被研究。数据将阐明小胶质细胞的一条重要的抑制信号通路，并将有助于理解CD33基因的多态性与阿尔茨海默病之间的联系。

Microglial cells can be polarized towards a pro- or anti-inflammatory phenotype, either leading to neuronal damage or brain repair. Recent data show that the immunoreceptor tyrosine-based inhibition motif (ITIM)-SHP1 tyrosine phosphatase signaling cascade contributes to an anti-inflammatory phenotype of microglia. In this project we will use microglial cells derived from mouse embryonic and human induced pluripotent stem cells as well as conditional SHP1 knock-out mice to study the ITIM-SHP1 function in microglia. Furthermore, the role of the human immunoreceptor CD33 for microglial ITIM-SHP1 signalling will be investigated. Data will elucidate an important inhibitory signalling pathway of microglia and will help to understand the association between a polymorphism of the CD33 gene and Alzheimer’s disease.