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Updated: Jul 17, 2026
Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
Published on: May 27, 2015
Cutting edge: both activating and inhibitory Fc receptors expressed on mast cells regulate experimental allergic
Michaela Robbie-Ryan1, Melinda B Tanzola, Virginia H Secor
1Graduate Program in Immunology and Molecular Pathogenesis, Emory University School of Medicine, Atlanta, GA 30322, USA.
Abstract:
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.
Insights
Mast cells significantly impact experimental allergic encephalomyelitis (EAE) severity. Activating and inhibitory Fc receptors (FcRs) on mast cells modulate EAE, influencing disease course and symptoms in this multiple sclerosis model.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Mast cells play a role in autoimmune diseases like multiple sclerosis.
- Experimental allergic encephalomyelitis (EAE) is a mouse model used to study multiple sclerosis.
- Fc receptors (FcRs) on mast cells are involved in immune responses.
Purpose of the Study:
- To investigate the role of Fc receptor-mediated mast cell activation in EAE.
- To determine how different FcRs on mast cells affect the severity and course of EAE.
Main Methods:
- Mast cell-deficient mice (W/W(v)) were reconstituted with bone marrow-derived mast cells (BMMCs) lacking specific FcRs.
- EAE was induced in reconstituted mice using myelin oligodendrocyte glycoprotein peptide.
- Clinical disease scores were analyzed and compared between groups.
Main Results:
- Mice reconstituted with FcRgamma or FcgammaRIII deficient BMMCs showed reduced EAE severity.
- Mice reconstituted with FcRIIB deficient BMMCs exhibited exacerbated EAE.
- FcgammaRIII deficiency in BMMCs led to a relapsing-remitting EAE course.
Conclusions:
- Both activating and inhibitory FcRs on mast cells are critical in modulating EAE.
- Mast cell FcRs represent potential therapeutic targets for multiple sclerosis.
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