Immunotherapy using lipopolysaccharide-stimulated bone marrow-derived dendritic cells to treat experimental autoimmune encephalomyelitis. (7th November 2014)

• Record Type: Journal Article
• Authors: Zhou, F; Ciric, B; Zhang, G-X; Rostami, A
• Is Part Of: Clinical and experimental immunology. Volume 178:Number 3(2014:Dec.)
• Page Start: 447
• Page End: 458
• Publication Date: 2014-11-07
• Subjects: CD4+T cell -- dendritic cell -- EAE -- immune tolerance -- immunotherapy; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12440
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: 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.