Journal
LABORATORY INVESTIGATION
Volume 91, Issue 4, Pages 627-641Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.2011.3
Keywords
C-kit mutations; experimental autoimmune encephalomyelitis; granulocytes; mast cells
Categories
Funding
- Italian Ministry of Health
- National Multiple Sclerosis Society New York
- Fondazione Italiana Sclerosi Multipla-FISM [2009/R/20]
- Associazione Italiana Ricerca sul Cancro
- My First AIRC [8726]
- Fondazione Italiana Sclerosi Multipla [2008/B/2]
- Fondazione Italiana Ricerca sul Cancro
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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
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