Kit (W-sh) mice develop earlier and more severe experimental autoimmune encephalomyelitis due to absence of immune suppression

Hongmei Li, Bardia Nourbakhsh, Farinaz Safavi, Ke Li, Hui Xu, Melissa Cullimore, Fang Zhou, Guangxian Zhang, Abdolmohamad Rostami

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Mast cells (MCs) have been thought to play a pathogenic role in the development of autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. However, an immunoregulatory function of these cells has recently been suggested. We investigated the role of MCs in EAE using the W-sh mouse strain, which is MC deficient. W-sh mice developed earlier and more severe clinical and pathological disease with extensive demyelination and inflammation in the CNS. The inflammatory cells were mainly composed of CD4+ T cells, monocyte/macrophages, neutrophils, and dendritic cells. Compared with wild-type mice, MC-deficient mice exhibited an increased level of MCP-1/CCR2 and CD44 expression on CD4+ T cells in addition to decreased production of regulatory T cells, IL-4, IL-5, IL-27, and IL-10. We also found that levels of IL-17, IFN-γ, and GM-CSF were significantly increased in peripheral lymphocytes from immunized W-sh mice compared with those in peripheral lymphocytes from wild-type mice. Reconstitution of W-sh mice downregulated susceptibility to EAE, which correlated with MC recruitment and regulatory T cell activation in the CNS. These findings indicate that responsiveness is not required in the pathogenesis of inflammatory demyelination in the CNS and that, in the absence of MCs, increased MCP-1, CCR2, IL-17, IFN-γ, CD44, and other inflammatory molecules may be responsible for increased severity of EAE.

Original languageEnglish (US)
Pages (from-to)274-282
Number of pages9
JournalJournal of Immunology
Volume187
Issue number1
DOIs
StatePublished - Jul 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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