Cutting edge: both activating and inhibitory Fc receptors expressed on mast cells regulate experimental allergic encephalomyelitis disease severity.
Mast cell-deficient mice (W/W(v)) exhibit significantly reduced severity of experimental allergic encephalomyelitis (EAE), a murine model of multiple sclerosis. In this study, the contribution of FcR-mediated mast cell activation to disease was examined. W/W(v) mice were reconstituted i.v. with bone marrow-derived mast cells (BMMCs) from wild-type mice or those lacking functional FcRs. Eight weeks later, EAE was induced by immunization with the myelin oligodendrocyte glycoprotein 35-55 peptide. Disease scores were analyzed in reconstituted mice and compared with age-matched W/W(v) mice and wild-type littermates. Mice reconstituted with FcRgamma(-/-) BMMCs or FcgammaRIII(-/-) BMMCs exhibited less severe clinical symptoms similar to W/W(v) controls, while reconstitution with FcRIIB(-/-) BMMCs resulted in disease significantly more severe than wild-type controls. Notably, mice reconstituted with FcgammaRIII(-/-) BMMC exhibit a relapsing-remitting course of disease. These data demonstrate that both activating and inhibitory FcRs expressed on mast cells influence the course of EAE.
Robbie-Ryan
Michaela
M
Graduate Program in Immunology and Molecular Pathogenesis, Emory University School of Medicine, Atlanta, GA 30322, USA.
Tanzola
Melinda B
MB
Secor
Virginia H
VH
Brown
Melissa A
MA
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000453:epidemiology / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D000939:Epitopes / Q000276:immunology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015994:Incidence; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D011961:Receptors, Fc / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012720:Severity of Illness Index
D001323:Autoantibodies; D000939:Epitopes; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011961:Receptors, Fc