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 FcRγ^-/- BMMCs or FcγRIII^-/- 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 FcγRIII^-/- 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.