Induction of Experimental Autoimmune Encephalomyelitis inMast cell‐Deficient Mice: Mast Cell Responsiveness Is NotRequired in the Pathogenesis of Inflammatory Demyelinationin the Central Nervous System

Mast cells were thought to be involved in the susceptibility to experimental autoimmune encephalomyelitis (EAE), a Th1 cell‐mediated autoimmune disorder of the CNS, are an important source of several mediators, including proteases and vasoactive amines, and can produce TNFa and IL‐4, respectively. Contrary to the expectation that the absence of mast cell would protect from EAE, we found that mast cell‐deficient mice (W ‐sh ) developed earlier and more severe disease, with extensive demyelination and CNS inflammation. The inflammatory cells were mainly comprised of CD4+T cells, monocyte/macrophages, and dendritic cells (DCs). Compared to wild‐type mice, mast cell‐deficient mice exhibited significantly increased autoantigen‐induced proliferative response, increased chemokine monocyte chemoattractant protein‐1(MCP‐1), IL‐2, and CD44 expression on CD4 T cells, besides , decreased production of Treg, GM‐CSF, IL‐4, IL‐5, IL‐27 and IL‐10. In addition, we found significantly increased levels of CCR2, IL‐17 and IL‐2 expression in spleen cells from immunized mast cell −/− mice compared with wild‐type mice. These findings indicate that responsiveness is not required in the pathogenesis of inflammatory demyelination in the CNS, and that, in the absence of mast cell, increased MCP‐1, CCR2, IL‐17, IL‐2, CD44 and other inflammatory molecules may be responsible for increased severity of EAE.