Fcgamma receptor-ligating complexes improve the course of experimental autoimmune encephalomyelitis by enhancing basal Th2 responses.
IL-12p40 and macrophages are essential for the induction of disease in the mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis. In this paper, we show that treatment of mice with opsonized erythrocytes, which have been shown to ligate Fcgamma receptors on macrophages and alter their cytokine profile, significantly delayed the onset of experimental autoimmune encephalomyelitis. This protection correlated to the induction of Th2 responses by autoreactive T cells, enhanced basal systemic responses and a significant downregulation of IL-12p40 and nitric oxide synthase-2, but not IFN-gamma expression. IL-4 was essential for the protection by opsonized erythrocytes as the effects of treatment were eliminated in IL-4-deficient mice. Together these studies suggest that the ligation of Fcgamma receptors can modify the development of autoimmune disease by altering macrophage activation and enhancing Th2 responses.
La Flamme
Anne C
AC
School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand. anne.laflamme@vuw.ac.nz
Harvie
Marina
M
McNeill
Andrea
A
Goldsack
Lisa
L
Tierney
Joanna B
JB
Bäckström
B Thomas
BT
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D007136:Immunoglobulins / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D017452:Receptors, IgG / Q000378:metabolism*; D012756:Sheep; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D007136:Immunoglobulins; D017452:Receptors, IgG; D018664:Interleukin-12; D015847:Interleukin-4