T cell - DAM feedback loop drives CNS inflammation and neurodegenration in SPG15 at an early age via CCR5-CCL5 interaction [CD3+]

The immune system is an emerging cause of neuroinflammation and is suspected to be involved in neurodegeneration. The role of microglia, the macrophages of the Central Nervous System (CNS), was extensively researched in CNS neuropathologies. However, we only start to understand the role of T cells in diseases like Alzheimer’s Disease (AD) and Huntington’s Disease (HD) and how microglial – T cell crosstalk contributes to these pathologies. Here we tackle these topics in a rare and less investigated disease called Spastic Paraplegia 15 (SPG15) using a Zfyve26-/- mouse model. We were able to show, that CD8+ T cells and microglia potentiate a pro-inflammatory response through bidirectional communication in SPG15 KO and not WT mouse brains. The increase of CD8+ T cells in SPG15 KO animals also required a TCR dependent component. These findings are in line with previous reports on neurodegenerative disease which hints at cross-condition mechanisms involved in CD8+T cell responses in CNS, when encountering accumulation of non-degradable material in the brain.