Tu196 - Epigenetic Regulation of Microglia and Infiltrating Myeloid Cells in the Central Nervous System of Mice with Experimental Autoimmune Encephalomyelitis

Abstract Text:

Introduction: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS), causing damage to myelin, oligodendrocytes, and axons. Early stages involve lymphocyte and macrophage infiltration into the CNS, persisting at reduced levels later. Microglia, the CNS’s tissue-resident macrophages, are activated early and become increasingly involved as the disease progresses. Their role in MS is complex, balancing pro-inflammatory activity with benefits like phagocytosing neurotoxins and myelin debris, and supporting oligodendrocyte progenitor cells. This study investigates longitudinal changes in microglia and infiltrating myeloid cells in the CNS of mice with experimental autoimmune encephalomyelitis (EAE), an archetypical MS animal model.

Methods: We collected microglia and myeloid cells from the CNS at four stages (baseline, acute, remission, chronic) in SJL/JRj mice with EAE. DNA and RNA were isolated for methylation analysis and bulk RNAseq, respectively.

Results: Analysis of DNA samples using SeSAMe identified 9504 (delta-beta ≥ 0.1; FDR ≤ 0.05) and 11524 (delta-beta ≥ 0.2; FDR ≤ 0.05) differentially methylated positions in microglia and myeloid cells, respectively. A heatmap visualized and clustered the data. Gene ontology analysis was conducted with GREAT, and transcription factor binding motif enrichment was analysed using HOMER. Bulk RNAseq is currently being analysed with results expected soon.

Conclusions: Significant changes were observed during the acute phase and progression to chronic phase, affecting genes involved in microglia and myeloid cell activation during clinical relapse in the EAE model. In vitro validations of our results are presently being set up to continue our research.