Interferon β induces mature dendritic cell apoptosis through caspase-11/caspase-3 activation

Abstract

Although interferon β (IFNβ) decreases relapse rate and disease activity in multiple sclerosis (MS), the mechanisms involved have not been elucidated. The present study is the first report on the apoptotic effect of IFNβ in mature, but not immature, myeloid dendritic cells (DCs). Both exogenous IFNβ added to DCs matured through exposure to proinflammatory cytokines and endogenous IFNβ secreted after lipopolysaccharide stimulation induced DC cell death. Apoptosis of mature DCs required both NF-κB and STAT-1 activation, and was mediated through the induction of caspase-11 expression and activation of caspase-3. In vivo, we observed increased caspase-11 expression and a significant decrease in the number of splenic DCs after lipopolysaccharide administration in wt but not in STAT-1–deficient mice. Since mature DCs are major contributors to the inflammatory response and essential partners in the induction of adaptive immunity, IFNβ-dependent elimination of activated DCs could play an essential role in re-establishing homeostasis, and might represent a new molecular mechanism for the therapeutic effect of IFNβ in MS.