title: Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient Kit W-sh/W-sh mice.
abstract: 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.
authors.affiliation: Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Piconese
authors.forename: Massimo
authors.initials: M
authors.lastname: Costanza
authors.forename: Silvia
authors.initials: S
authors.lastname: Musio
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Pietro L
authors.initials: PL
authors.lastname: Poliani
authors.forename: Giorgia
authors.initials: G
authors.lastname: Gri
authors.forename: Alessia
authors.initials: A
authors.lastname: Burocchi
authors.forename: Paola
authors.initials: P
authors.lastname: Pittoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Gorzanelli
authors.forename: Mario P
authors.initials: MP
authors.lastname: Colombo
authors.forename: Rosetta
authors.initials: R
authors.lastname: Pedotti
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001854:Bone Marrow Cells / Q000473:pathology; D002490:Central Nervous System / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D006023:Glycoproteins / Q000276:immunology; D006098:Granulocytes / Q000473:pathology; D007114:Immunization; D008407:Mast Cells / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009186:Myelin Sheath / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D019009:Proto-Oncogene Proteins c-kit