Selective depletion of CD11c+ CD11b+ dendritic cells partially abrogates tolerogenic effects of intravenous MOG in murine EAE.

Abstract

Intravenous (i.v.) injection of a soluble myelin antigen can induce tolerance, which effectively ameliorates experimental autoimmune encephalomyelitis (EAE). We have previously shown that i.v. myelin oligodendrocyte glycoprotein (MOG) induces tolerance in EAE and expands a subpopulation of tolerogenic CD11c+ CD11b+ dendritic cells (DCs) with an immature phenotype having low expression of IA and co-stimulatory molecules CD40, CD86, and CD80. Here, we further investigate the role of tolerogenic DCs in i.v. tolerance by injecting clodronate-loaded liposomes, which selectively deplete CD11c+ CD11b+ and immature DCs, but not CD11c+ CD8+ DCs and mature DCs. I.v. MOG-induced suppression of EAE was partially, yet significantly, blocked by CD11c+ CD11b+ DC depletion. While i.v. MOG inhibited IA, CD40, CD80, CD86 expression and induced TGF-β, IL-27, IL-10 production in CD11c+ CD11b+ DCs, these effects were abrogated after injection of clodronate-loaded liposomes. Depletion of CD11c+ CD11b+ DCs also precluded i.v. autoantigen-induced T-cell tolerance, such as decreased production of IL-2, IFN-γ, IL-17 and numbers of IL-2+ , IFN-γ+ , and IL-17+ CD4+ T cells, as well as an increased proportion of CD4+ CD25+ Foxp3+ regulatory T cells and CD4+ IL-10+ Foxp3- Tr1 cells. CD11c+ CD11b+ DCs, through low expression of IA and costimulatory molecules as well as high expression of TGF-β, IL-27, and IL-10, play an important role in i.v. tolerance-induced EAE suppression.

• Authors: Limei Wang, Zichen Li, Bogoljub Ciric, Farinaz Safavi, Guang-Xian Zhang, Abdolmohamad Rostami
• Journal: European journal of immunology (Eur J Immunol) Vol. 46 Issue 10 Pg. 2454-2466 (10 2016) ISSN: 1521-4141 [Electronic] Germany
• PMID: 27338697 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Chemical References

• CD11b Antigen
• CD11c Antigen
• Cytokines
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• Liposomes
• Myelin-Oligodendrocyte Glycoprotein
• Clodronic Acid

Topics

• Administration, Intravenous
• Animals
• CD11b Antigen (metabolism)
• CD11c Antigen (metabolism)
• Cell Differentiation
• Cells, Cultured
• Clodronic Acid (administration & dosage)
• Cytokines (metabolism)
• Dendritic Cells (immunology, pathology)
• Encephalomyelitis, Autoimmune, Experimental (immunology)
• Female
• Forkhead Transcription Factors (metabolism)
• Immune Tolerance
• Liposomes (administration & dosage)
• Lymphocyte Activation
• Mice
• Mice, Inbred C57BL
• Myelin-Oligodendrocyte Glycoprotein (immunology)
• T-Lymphocyte Subsets (immunology)
• T-Lymphocytes, Regulatory (immunology)