Intravenous transfer of apoptotic cell-treated dendritic cells leads to immune tolerance by blocking Th17 cell activity.

Apoptotic cell-induced tolerogenic dendritic cells (DCs) play an important role in induction of peripheral tolerance in vivo; however, the mechanisms of immune tolerance induced by these DCs are poorly understood. Here we show that treatment of apoptotic cells modulates expression of inflammation- and tolerance-associated molecules including Gr-1, B220, CD205 and galectin-1 on bone marrow-derived DCs. In addition, apoptotic cell-treated DCs suppress secretion of cytokines produced by Th17 cells. Our data also demonstrate that i.v. transfer of apoptotic cell-treated DCs blocks EAE development and down-regulates production of inflammatory cytokines such as IL-17A and IL-17F in CD4+ T cells. These results suggest that apoptotic cell-treated DCs may inhibit activity of Th17 cells via down-regulation of inflammatory cytokine production, thereby affecting EAE development in vivo. Our results reveal a potential mechanism of immune tolerance mediated by apoptotic cell-treated DCs and the possible use of apoptotic cell-treated DCs to treat autoimmune diseases such as MS/EAE.