W122 - Profiling of Immune Infiltrates in RR-EAE Reveals Dynamic Changes in Myeloid Cells

Christina Adler – Regeneron Pharmaceuticals; Gurinder Atwal – Regeneron Pharmaceuticals; Asiel Benitez – boehringer-ingelheim; Joseph Devlin – Regeneron Pharmaceuticals; Sokol Haxhinasto – Regeneron Pharmaceuticals; Weikeat Lim – Regeneron Pharmaceuticals; Jamie Orengo – Regeneron Pharmaceuticals; Matthew Sleeman – Regeneron Pharmaceuticals; Natalia Swiecki – Regeneron Pharmaceuticals

Abstract Text: Relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) is characterized by a pattern of relapses and spontaneous recovery occurring over a period of weeks to months. This pattern is very similar to the clinical signs of disease observed in multiple sclerosis (MS) patients over many years. The immune response in MS is primarily driven by autoreactive T lymphocytes that recognize myelin peptides. However, the mechanisms involved in the induction of the disease and clinical relapses are not well understood. To this end, we performed deep profiling of spinal cord and infiltrates at the different phases of the disease (onset, peak, remitting, and relapsing) using single-cell RNA sequencing and multi-parameter flow cytometry in SJL mice immunized with PLP139- 151. This line of experimentation revealed drastic changes in immune cell composition over time with unique cellular compositions revealed during the different disease phases. Further analysis uncovered marked changes in the number of myeloid cells such as macrophages, dendritic cells, and monocytes and respective subsets during each disease phase. In addition, the infiltrating myeloid cells had distinct transcriptional signatures which might define their role throughout the phases of the disease. Our comprehensive analysis of immune infiltrates identifies functional heterogeneity of key myeloid cell subsets that in concert with other cells could be contributing to disease pathogenesis.