Chloroquine‐treated dendritic cells require STAT1 signaling for their tolerogenic activity

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are T cell-driven autoimmune diseases of the central nervous system (CNS) where interleukin (IL)-17-producing Th17 cells promote damage and are pathogenic. Conversely, tolerogenic dendritic cells (DCs) induce regulatory T (Treg) cells and suppress Th17 cells. Chloroquine (CQ) suppresses EAE through the modulation of DCs by unknown mechanisms. Here we show that signal transducer and activator of transcription (STAT) 1 is necessary for CQ-induced tolerogenic DCs (tolDCs) to efficiently suppress EAE. We observed that CQ induces phosphorylation of STAT1 in DCs in vivo and in vitro. Genetic blockage of STAT1 abrogated the suppressive activity of CQ-treated DCs. Our findings show that STAT1 is a major signaling pathway in CQ-induced tolDCs and may shed light on new therapeutic avenues for the induction of tolDCs in autoimmune diseases, such as MS.