title: Immunotherapy using lipopolysaccharide-stimulated bone marrow-derived dendritic cells to treat experimental autoimmune encephalomyelitis.
abstract: Lipopolysaccharide (LPS) produced by Gram-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 (DCs) and modulates phenotypes of DCs. LPS treatment up-regulates expression of tolerance-associated molecules such as CD205 and galectin-1, but down-regulates expression of Gr-1 and B220 on CD11c(+) DCs. Moreover, LPS treatment regulates the numbers of CD11c(+) CD8(+) , CD11c(+) CD11b(low) and CD11c(+) CD11b(hi) DCs, which perform different immune functions in vivo. Our data also demonstrated that intravenous transfer of LPS-treated DCs blocks experimental autoimmune encephalomyelitis (EAE) development and down-regulates expression of retinoic acid-related orphan receptor gamma t (ROR-γt), interleukin (IL)-17A, IL-17F, IL-21, IL-22 and interferon (IFN)-γ in myelin oligodendrocyte glycoprotein (MOG)-primed CD4(+) T cells in the peripheral environment. These results suggest that LPS-induced apoptotic DCs may lead to generation of tolerogenic DCs and suppress the activity of MOG-stimulated effector CD4(+) T cells, thus inhibiting the development of EAE in vivo. Our results imply a potential mechanism of LPS-induced tolerance mediated by DCs and the possible use of LPS-induced apoptotic DCs to treat autoimmune diseases such as multiple sclerosis.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: F
authors.initials: F
authors.lastname: Zhou
authors.forename: B
authors.initials: B
authors.lastname: Ciric
authors.forename: G-X
authors.initials: GX
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Rostami
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000276:immunology*; D039481:CD11b Antigen / Q000032:analysis; D039521:CD11c Antigen / Q000032:analysis; D016207:Cytokines / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
chemical_list: D039481:CD11b Antigen; D039521:CD11c Antigen; D016207:Cytokines; D008070:Lipopolysaccharides
keywords: CD4+ T cell; EAE; dendritic cell; immune tolerance; immunotherapy