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

Publication/Presentation Date

12-1-2014

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.

Volume

178

Issue

3

First Page

447

Last Page

458

ISSN

1365-2249

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

25138204

Department(s)

Administration and Leadership

Document Type

Article

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