Comparative immune cell interactions in the central nervous system in autoimmunity and brain tumors

• Applicant: Dr. Michael Kilian
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases ; Immunology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 515853030

Even though the central nervous system (CNS) has been described as an immune-privileged organ, recent research has shown significant infiltration of immune cells in CNS diseases like multiple sclerosis (MS) or brain tumors. For both diseases, a strong dependency for T cells has been described, with a significant impact of CD4 T cell to the immune response. However, it remains unclear why T cell responses are maintained in autoimmunity like MS and are impaired and dysfunctional in brain tumors. CNS-resident CD4 T cells have recently been described and have been shown to be crucial for microglial development, however the role of CNS-resident CD4 T cells has not yet been investigated in the context of CNS diseases. We hypothesize that CNS-resident CD4 T cells are essential for the immune response in early disease onset and aim to decipher their role in maintaining functional or dysfunctional immune responses in MS and brain tumors via immune cell interactions. Building on the previously developed technology to analyze physical cell-cell interactions and transcriptomic changes on a single-cell level (RABID-Seq), we will perform a comprehensive screen to characterize cell-cell interactions and downstream signaling between CNS-resident cells and other immune cells in murine models of MS and brain tumors. In order to validate their functional relevance, convergent and disease-exclusive interactions will be disturbed using in vivo knockdowns in both disease models. Identified immune cell interactions will be validated in human MS and glioblastoma tissue using RNA-ish, flow cytometry and human cell-cell interaction screens. The results of this study will provide in depth mechanistical insight into cell-cell interactions in CNS diseases potentially leading to novel targets that can be harnessed for the treatment of brain tumor or MS patients.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Francisco Quintana