Immunotherapy using lipopolysaccharide‐stimulated bone marrow‐derived dendritic cells to treat experimental autoimmune encephalomyelitis

Summary Lipopolysaccharide ( LPS) produced by G ram‐negative bacteria induces tolerance and suppresses inflammatory responses in vivo; however, the mechanisms are poorly understood. In this study we show that LPS induces apoptosis of bone marrow‐derived dendritic cells ( DC s) and modulates phenotypes of DC s. LPS treatment up‐regulates expression of tolerance‐associated molecules such as CD 205 and galectin‐1, but down‐regulates expression of G r‐1 and B 220 on CD 11c + DC s. Moreover, LPS treatment regulates the numbers of CD 11c + CD 8 + , CD 11c + CD 11b low and CD 11c + CD 11b hi DC s, which perform different immune functions in vivo . Our data also demonstrated that intravenous transfer of LPS ‐treated DC s blocks experimental autoimmune encephalomyelitis (EAE) development and down‐regulates expression of retinoic acid‐related orphan receptor gamma t (ROR ‐γt), interleukin ( IL) ‐17 A , IL ‐17 F , IL ‐21, IL ‐22 and interferon ( IFN) ‐γ in myelin oligodendrocyte glycoprotein (MOG) ‐primed CD 4 + T cells in the peripheral environment. These results suggest that LPS ‐induced apoptotic DC s may lead to generation of tolerogenic DC s and suppress the activity of MOG ‐stimulated effector CD 4 + T cells, thus inhibiting the development of EAE   in vivo . Our results imply a potential mechanism of LPS ‐induced tolerance mediated by DC s and the possible use of LPS ‐induced apoptotic DC s to treat autoimmune diseases such as multiple sclerosis.