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. Laboratory Investigation (2011) 91, 627-641; doi:10.1038/labinvest.2011.3; published online 14 February 2011

Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient Kit(W-sh/W-sh) mice / Piconese, Silvia; Massimo, Costanza; Silvia, Musio; Claudio, Tripodo; Pietro L., Poliani; Giorgia, Gri; Alessia, Burocchi; Paola, Pittoni; Andrea, Gorzanelli; Mario P., Colombo; Rosetta, Pedotti. - In: LABORATORY INVESTIGATION. - ISSN 0023-6837. - 91:4(2011), pp. 627-641. [10.1038/labinvest.2011.3]

Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient Kit(W-sh/W-sh) mice

PICONESE, SILVIA;
2011

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. Laboratory Investigation (2011) 91, 627-641; doi:10.1038/labinvest.2011.3; published online 14 February 2011
2011
c-kit mutations; experimental autoimmune encephalomyelitis; granulocytes; mast cells
01 Pubblicazione su rivista::01a Articolo in rivista
Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient Kit(W-sh/W-sh) mice / Piconese, Silvia; Massimo, Costanza; Silvia, Musio; Claudio, Tripodo; Pietro L., Poliani; Giorgia, Gri; Alessia, Burocchi; Paola, Pittoni; Andrea, Gorzanelli; Mario P., Colombo; Rosetta, Pedotti. - In: LABORATORY INVESTIGATION. - ISSN 0023-6837. - 91:4(2011), pp. 627-641. [10.1038/labinvest.2011.3]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/382307
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