PROJECT: JTC2024 - Brain-Body: MICE-AE

Autoimmune encephalitis (AIE) is a paradigmatic inflammatory brain disease with autoantibodies targeting specific neuronal and glial antigens. The cause of AIE is largely unknown, but we have previously identified links between mucosal barriers, microbiota, and brain autoimmunity. The consortium will investigate the microbiota-immune brain interaction in the pathogenesis of AIE. The overarching hypothesis is that conventional neuronal/glial autoantigen-specific T-cells, together with a loss of systemic and intrathecal regulatory mechanisms mediated by innate-like MAIT cells, promote the extraordinary plasma cell expansion and autoantibody production observed in AIE. The work packages include characterising the meningeal and parenchymal MAIT cell expansion, exploring the regulation of autoantibody formation by intestinal microbiota and MAIT cells. We will also identify candidate microbial epitopes and further develop a mouse model of AIE to confirm the functional relevance of MAIT cells in this process. The research team will combine cutting-edge technologies including spatial transcriptomics in autopsy tissue, single-cell RNA sequencing, flow cytometry, T-cell receptor characterization, metagenomics, and murine immunisation models to investigate the microbiota-immune brain interaction in the pathogenesis of AIE. The ultimate goal of this research is to identify new treatments to improve patient outcomes by improving our understanding of AIE.