title: Kit (W-sh) mice develop earlier and more severe experimental autoimmune encephalomyelitis due to absence of immune suppression.
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.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.forename: Bardia
authors.initials: B
authors.lastname: Nourbakhsh
authors.forename: Farinaz
authors.initials: F
authors.lastname: Safavi
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Melissa
authors.initials: M
authors.lastname: Cullimore
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Guangxian
authors.initials: G
authors.lastname: Zhang
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D007108:Immune Tolerance / Q000235:genetics* / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D019009:Proto-Oncogene Proteins c-kit / Q000172:deficiency* / Q000235:genetics; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology
chemical_list: C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D019009:Proto-Oncogene Proteins c-kit