IFN-β and multiple sclerosis: Cross-talking of immune cells and integration of immunoregulatory networks

• IFN-β therapy stimulates intra- and inter-cellular networks regulating immune responses.
• IFN-β therapy promotes an anti-inflammatory status in MS patients.
• IFN-β therapy regulates pathogenic immune cell subsets by modulating bystander responses.
• IFN-β effectiveness in MS may rely on both immunomodulatory and anti-viral effects.

Multiple sclerosis (MS) is characterized by autoimmune inflammation affecting the central nervous system and subsequent neurodegeneration.Historically, damage was thought to be mediated exclusively by auto-antigen-activated pro-inflammatory T cells. However, more recently, we are gaining increasing knowledge on the pathogenic role played in MS by B cells, dendritic cells and monocytes.IFN-β therapy was one the first approved therapy for MS for its ability to reduce relapse rate and MRI lesion activity and to significantly decrease risk of disability progression.IFN-β-mediated mechanisms of action, even if not completely understood, mainly rely on its multifaceted pleiotropic effects resulting in sustained anti-inflammatory properties directed toward almost every immune cell type.Here, we will discuss in detail literature data characterizing the pathogenic activity of the different immune cell subsets involved in MS pathogenesis and how IFN-β therapy regulates their function by modulating bystander responses.We believe that the effectiveness of this drug in MS treatment, even if in use for a long time, can unveil new insights on this disease and still teach a lesson to researchers in the MS field.