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Innate Immunity: Mechanisms and Modulation | EK39


The role of microglia in Relapsing-Remitting EAE


Apr 12, 2021 12:00am ‐ Apr 12, 2021 12:00am

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The role of microglia in Relapsing-Remitting EAE Zhana Haimon1, Louise Chappel-Maor1, Steffen Jung1 Microglia are the resident mononuclear phagocytes of the central nervous system (CNS) parenchyma, sequestered behind the blood brain barrier (BBB). Exact functional contributions of microglia in CNS pathologies remain unclear due to difficulties in discriminating resident microglia from infiltrating monocyte-derived macrophages. Using the RiboTag strategy, we longitudinally profiled microglial translatomes throughout the stages of a Relapsing-Remitting Experimental Autoimmune Encephalomyelitis (RR-EAE) mouse model of multiple sclerosis (MS) in (SJL*B6) F1 hybrid mice challenged with PLP peptide. We show that microglia translate transcripts related to cell-cell immune interactions, alongside inhibitory molecules such as IL-18bp, Lag3, and PDL-1, at peak of disease prior to remission. Depletion of microglia in Cx3cr1CreER:Rosa26iDTR mice led to delayed recovery which was accompanied by accumulation of T cells in the brain, suggesting a protective role of microglia in RR-EAE. Using advanced image-stream analysis, multicolor immunofluorescence and flow cytometry, we found evidence for cognate microglia interactions with T cells, and preferentially T regulatory (Treg) cells. Collectively our results propose that microglia play a protective role in EAE, by cognate interactions with Treg cells in the brain. 1 Immunology department, Weizmann Institute of Science, Rehovot, Israel

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