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

Author:

Zhou F12,Ciric B1,Zhang G-X1,Rostami A1

Affiliation:

1. Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA

2. Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation (OMRF), 825, NE 13th Street, Oklahoma City, OK, 73104, USA

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+ CD11blow and CD11c+ CD11bhi 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.

Funder

NIH

National Multiple Sclerosis Society

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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