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

Growing evidence are showing a pivotal role of macrophages (MФ) and microglia (MG) in the pathogenesis of Multiple sclerosis (MS). Interferon β (IFN β) 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 β therapeutic effect. Our sorted MФ/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. Analysis of differentially expressed genes in WT and KO myeloid cells isolated from spinal cords of mice with neuroinflammation