Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient KitW-sh/W-sh mice

Abstract

Mast cell (MC)-deficient c-Kit mutant KitW/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, KitW-sh/W-sh. Surprisingly, we observed that myelin oligodendrocyte glycoprotein (MOG)35–55-induced chronic EAE was exacerbated in KitW-sh/W-sh compared with Kit+/+ mice. KitW-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 KitW-sh/W-sh and in KitW/W-v mice were because of the different immunization protocols, we induced EAE in these two strains with varying doses of MOG35–55 and adjuvants. Although KitW-sh/W-sh mice exhibited exacerbated EAE under all immunization protocols, KitW/W-v mice were protected from EAE only when immunized with high, but not low, doses of antigen and adjuvants. KitW-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 KitW-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.