Project Details
Projekt
Decoding IL-17A-mediated influences on stroke recovery
Subject Area
Molecular and Cellular Neurology and Neuropathology
Experimental Models for the Understanding of Nervous System Diseases
Experimental Models for the Understanding of Nervous System Diseases
Term
since 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 405358801
In stroke, the highly conserved cytokine IL-17A is pivotal for the amplification of the detrimental postischemic inflammatory response in the ischemic tissue. At the same time, IL-17A holds important non-immune properties with trophic and homeostatic effects on neurons and glial cells. Although the immune-pathogenic role of IL-17A has clearly been shown in stroke, it is currently unknown whether different CNS-resident cells differentially sense and react to IL-17A and thereby determine neuronal regeneration. Therefore, the overall objective of the project is to understand how the highly conserved cytokine IL-17A dictates stroke outcome. We aim to decipher the cellular source of IL-17A in the ischemic brain tissue and whether IL-17A dictates neuronal and astrocytic signaling pathways, which alter cellular gene networks that influence neuronal functions. To do so, we will follow the long-term phenotypic outcome after experimental stroke and combine that with cell-type-specific deletions of IL17A and its receptor and cell-type-specific transcriptomics. Eventually, newly assembled gene networks will be validated and mechanistically explored in mouse and human neuronal cell cultures challenged with glutamate and oxygen-glucose deprivation. Thus, we expect to identify neuron-intrinsic genes that are directly regulated by IL-17A or indirectly by astrocytic output after sensing IL-17A and that determine stoke outcome. We envision that these could be potential drug targets to improve post-stroke regeneration.
DFG Programme
Research Units
