6533b86cfe1ef96bd12c819e
RESEARCH PRODUCT
Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient KitW-sh/W-sh mice
Pietro Luigi PolianiSilvia PiconeseRosetta PedottiSilvia MusioAndrea GorzanelliGiorgia GriMario P. ColomboPaola PittoniAlessia BurocchiClaudio TripodoMassimo Costanzasubject
Central Nervous SystemT-LymphocytesEncephalomyelitisexperimental autoimmune encephalomyelitismast cellsInbred C57BLSeverity of Illness IndeximmunologyMiceMyelinPeptide Fragmentimmune system diseasesMast CellEncephalomyelitisMyelin SheathbiologyExperimental autoimmune encephalomyelitisMast cellProto-Oncogene Proteins c-kitPhenotypemedicine.anatomical_structuremastcell-deficient miceBone Marrow Cellgenetics/immunology/pathology/prevention /&/ controlc-kit mutationsc-kit mutations; experimental autoimmune encephalomyelitis; granulocytes; mast cellsEncephalomyelitis Autoimmune ExperimentalCentral nervous systemBone Marrow CellsPathology and Forensic MedicineMyelin oligodendrocyte glycoproteinExperimentalAnimals Antibody Formation Bone Marrow Cells; pathology Central Nervous System; pathology Encephalomyelitis; Autoimmune; Experimental; genetics/immunology/pathology/prevention /&/ control Glycoproteins; immunology Granulocytes; pathology Immunization Mast Cells; pathology Mice Mice; Inbred C57BL Mutation Myelin Sheath; immunology Myelin-Oligodendrocyte Glycoprotein Peptide Fragments; immunology Phenotype Proto-Oncogene Proteins c-kit; deficiency/genetics/metabolism Severity of Illness Index T-Lymphocytes; pathologyAntigendeficiency/genetics/metabolismmedicineAnimalsMolecular BiologyGlycoproteinsAnimalMultiple sclerosismast-cell-deficient Kit W-sh/W-sh mice.Experimental autoimmune encephalomyelitis; mast-cell-deficient Kit W-sh/W-sh mice.GranulocytegranulocytesCell Biologymedicine.diseaseEncephalomyelitiExperimental autoimmune encephalomyelitiPeptide FragmentsMice Inbred C57BLT-LymphocyteAntibody FormationMutationImmunologybiology.proteinexperimental autoimmune encephalomyelitis; mastcell-deficient mice; mast cellspathologyImmunizationMyelin-Oligodendrocyte GlycoproteinGlycoproteinAutoimmunedescription
Mast cell (MC)-deficient c-Kit mutant Kit(W/W-v) mice are protected against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, suggesting a detrimental role for MCs in this disease. To further investigate the role of MCs in EAE, we took advantage of a recently characterized model of MC deficiency, Kit(W-sh/W-sh). Surprisingly, we observed that myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE was exacerbated in Kit(W-sh/W-sh) compared with Kit(+/+) mice. Kit(W-sh/W-sh) mice showed more inflammatory foci in the central nervous system (CNS) and increased T-cell response against myelin. To understand whether the discrepant results obtained in Kit(W-sh/W-sh) and in Kit(W/W-v) mice were because of the different immunization protocols, we induced EAE in these two strains with varying doses of MOG(35-55) and adjuvants. Although Kit(W-sh/W-sh) mice exhibited exacerbated EAE under all immunization protocols, Kit(W/W-v) mice were protected from EAE only when immunized with high, but not low, doses of antigen and adjuvants. Kit(W-sh/W-sh) mice reconstituted systemically, but not in the CNS, with bone marrow-derived MCs still developed exacerbated EAE, indicating that protection from disease could be exerted by MCs mainly in the CNS, and/or by other cells possibly dysregulated in Kit(W-sh/W-sh) mice. In summary, these data suggest to reconsider MC contribution to EAE, taking into account the variables of using different experimental models and immunization protocols.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-04-01 | Laboratory Investigation |