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

Silvia Piconese, Massimo Costanza, Silvia Musio, Claudio Tripodo, Pietro L. Poliani, Giorgia Gri, Alessia Burocchi, Paola Pittoni, Andrea Gorzanelli, Mario P. Colombo, Rosetta Pedotti

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)627-641
Number of pages15
JournalLaboratory Investigation
Volume91
Issue number4
DOIs
Publication statusPublished - Apr 2011

Keywords

  • C-kit mutations
  • experimental autoimmune encephalomyelitis
  • granulocytes
  • mast cells

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient Kit W-sh/W-sh mice'. Together they form a unique fingerprint.

  • Cite this

    Piconese, S., Costanza, M., Musio, S., Tripodo, C., Poliani, P. L., Gri, G., Burocchi, A., Pittoni, P., Gorzanelli, A., Colombo, M. P., & Pedotti, R. (2011). Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient Kit W-sh/W-sh mice. Laboratory Investigation, 91(4), 627-641. https://doi.org/10.1038/labinvest.2011.3