GSE169670
IFN-b acts on monocytes to ameliorate CNS autoimmunity by inhibiting proinflammatory cross-talk between monocytes and Th cells
Multiple sclerosis (MS) has been treated with IFN-b for three decades, but the mechanisms underlying its beneficial effects are not well understood. Our study elucidates, in a mouse model of MS, a potential mechanism whereby IFN-b inhibits cooperation between monocytes and T cells, two key immune cell types in MS. We found that IFN-b acts on monocytes to induce secretion of anti-inflammatory molecules, IL-10 and TGF-b, which act on T cells to suppress their production of pro-inflammatory molecules, GM-CSF, TNF, and FASL. Given that these T cell molecules induce proinflammatory features of monocytes, such as IL-1b production, we concluded that IFN-b therapy suppresses cooperation between monocytes and T cells, which otherwise reciprocally amplifies their harmful roles in MS. Overall design: WT/IFNAR1-/- mix bone marrow chimera mice were generated, immunized for EAE induction, and treated with IFN-b daily. WT and IFNAR1-/- monocytes were isolated and their transcriptome were analyzed by RNA sequencing