Anti-Inflammatory Polarization of Microglia by ITIM-SHP1 Signalling

• Applicant: Professor Dr. Harald Neumann
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2010 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 140392386

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.

• DFG Programme: Research Units
• Subproject of: FOR 1336: From Monocytes to Brain Macrophages - Conditions Influencing the Fate of Myeloid Cells in the Brain