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

Lab Invest. 2011 Apr;91(4):627-41. doi: 10.1038/labinvest.2011.3. Epub 2011 Feb 14.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • Bone Marrow Cells / pathology
  • Central Nervous System / pathology
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Encephalomyelitis, Autoimmune, Experimental / 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*
  • Proto-Oncogene Proteins c-kit / genetics*
  • Proto-Oncogene Proteins c-kit / metabolism
  • Severity of Illness Index
  • T-Lymphocytes / pathology

Substances

  • Glycoproteins
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-55)
  • Proto-Oncogene Proteins c-kit