Transcriptionnal coregulator GRIP1 differentially modulate myeloid cell-driven neuroinflammation and response to IFN-beta therapy

Growing evidence are showing a pivotal role of macrophages (M?) and microglia (MG) in the pathogenesis of Multiple sclerosis (MS). Interferon ß (IFN ß) and glucocorticoids are front line treatments in MS, and disrupting either type I IFN or GC receptor (GR) pathway in mice aggravates EAE, the mouse model of MS. Here, we evaluated GR Interacting Protein 1 actions in neuroinflammation by subjecting mice conditionally lacking GRIP1 in myeloid cells (cKO) to EAE. We showed that myeloid GRIP1 plays a dual role by promoting the 'effector' neuroinflammatory phase of EAE as well as mediating IFN ß therapeutic effect. Our sorted M?/MG transcriptome analysis reveals dramatic changes in inflammatory and IFN-pathway gene expression including potential differences of GRIP1 function in these distinct myeloid cell populations. Overall design: Analysis of differentially expressed genes in WT and KO myeloid cells isolated from spinal cords of mice with neuroinflammation