IFNβ promotes the conversion of pro-inflammatory M1-like into anti-inflammatory M2-like microglia (171.14)

Abstract

Abstract IFNβ is an approved therapeutic option for the treatment of certain autoimmune diseases such as MS/EAE. However, the molecular mechanisms underlying the effects of IFNβ in MS/EAE are not fully understood. In this study, we identified a novel mechanism for the beneficial effect of IFNβ in MS/EAE through the conversion of microglia (MG) from pro-inflammatory M1-like (MG1) to anti-inflammatory M2-like (MG2). Our results show that IFNβ inhibits expression and production of proinflammatory M1-type cytokines, such as IL-12p40, IL-23 and TNFα and promotes the anti-inflammatory M2 cytokine IL-10 in LPS-stimulated primary MG. In addition, IFNβ treatment also enhanced the expression of specific M2 makers, such as arginase and YM-1. Through this phenotype switch, IFNβ-treated MG suppressed Th1 and Th17 activation leading to the downregulation of IFNγ and IL-17. In vivo, IFNβ-treated EAE mice exhibit lower clinical scores, reduced Iba-1, IFNγ and IL-17 expression, and increased expression of the M2 markers, arginase, YM-1 and IL-10 in the CNS. Taken altogether, our results demonstrate that IFNβ favors the generation of MG2 leading to the secretion of the anti-inflammatory cytokine IL-10 and reduced expression of the pro-inflammatory cytokines, IL-12, IL-23, IFNγ and IL-17 in vitro and in vivo.