title: Type II-activated macrophages suppress the development of experimental autoimmune encephalomyelitis.
abstract: Treatment with immune complexes, which ligate Fcgamma receptors (FcgammaRs), suppresses the development of experimental autoimmune encephalomyelitis (EAE). To determine the mechanism of action, we investigated how these immune complexes affected type II activation of macrophages (that is, exposure to immune complexes in a proinflammatory environment). Our results show that lower doses of interferon-gamma (IFN-gamma) were more effective at priming bone marrow-derived macrophages (BMMphi) to produce more interleukin 10 (IL-10) and less IL-12p40 in response to lipopolysaccharide (LPS) and immune complexes compared with LPS alone. Moreover, at the lowest level of IFN-gamma (20 U ml(-1)), a significant downregulation in the surface expression of CD40, CD80 and PD-L1 was observed in LPS and immune complex-stimulated macrophages (that is, type II activated) than macrophages stimulated with LPS alone (that is, classically activated). Finally, treatment of mice with type II-activated macrophages protected them from developing EAE, suggesting that administration of immune complexes is protective against EAE by inducing type II-activated macrophages.
authors.affiliation: School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Tierney
authors.forename: Marie
authors.initials: M
authors.lastname: Kharkrang
authors.forename: Anne Camille
authors.initials: AC
authors.lastname: La Flamme
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000008:administration & dosage*; D018122:B7-1 Antigen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D060890:B7-H1 Antigen; D019013:CD40 Antigens / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D006023:Glycoproteins / Q000494:pharmacology; D007155:Immunologic Factors / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D019013:CD40 Antigens; C498919:Cd274 protein, mouse; D006023:Glycoproteins; D007155:Immunologic Factors; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010455:Peptides; D017452:Receptors, IgG; C526792:myelin oligodendrocyte glycoprotein (35-50), Ala(37)-; D016753:Interleukin-10; D007371:Interferon-gamma