Myeloid-derived suppressor cells as a potential therapy for experimental autoimmune myasthenia gravis.

Abstract

We recently demonstrated that hepatic stellate cells induce the differentiation of myeloid-derived suppressor cells (MDSCs) from myeloid progenitors. In this study, we found that adoptive transfer of these MDSCs effectively reversed disease progression in experimental autoimmune myasthenia gravis (EAMG), a T cell-dependent and B cell-mediated model for myasthenia gravis. In addition to ameliorated disease severity, MDSC-treated EAMG mice showed suppressed acetylcholine receptor (AChR)-specific T cell responses, decreased levels of serum anti-AChR IgGs, and reduced complement activation at the neuromuscular junctions. Incubating MDSCs with B cells activated by anti-IgM or anti-CD40 Abs inhibited the proliferation of these in vitro-activated B cells. Administering MDSCs into mice immunized with a T cell-independent Ag inhibited the Ag-specific Ab production in vivo. MDSCs directly inhibit B cells through multiple mechanisms, including PGE2, inducible NO synthase, and arginase. Interestingly, MDSC treatment in EAMG mice does not appear to significantly inhibit their immune response to a nonrelevant Ag, OVA. These results demonstrated that hepatic stellate cell-induced MDSCs concurrently suppress both T and B cell autoimmunity, leading to effective treatment of established EAMG, and that the MDSCs inhibit AChR-specific immune responses at least partially in an Ag-specific manner. These data suggest that MDSCs could be further developed as a novel approach to treating myasthenia gravis and, even more broadly, other diseases in which T and B cells are involved in pathogenesis.

• Authors: Yan Li, Zhidan Tu, Shiguang Qian, John J Fung, Sanford D Markowitz, Linda L Kusner, Henry J Kaminski, Lina Lu, Feng Lin
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 193 Issue 5 Pg. 2127-34 (Sep 01 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 25057008 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 by The American Association of Immunologists, Inc.

Chemical References

• Autoantibodies
• Immunoglobulin G
• Immunoglobulin M
• Receptors, Nicotinic
• Dinoprostone

Topics

• Animals
• Autoantibodies (immunology)
• B-Lymphocytes (immunology, pathology)
• Dinoprostone (immunology)
• Hepatic Stellate Cells (immunology, pathology)
• Immunoglobulin G (immunology)
• Immunoglobulin M (immunology)
• Mice
• Myasthenia Gravis, Autoimmune, Experimental (immunology, pathology, therapy)
• Myeloid Cells (immunology, pathology, transplantation)
• Receptors, Nicotinic (immunology)
• T-Lymphocytes (immunology, pathology)