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Roles of mast cells in the pathogenesis of inflammatory myopathy.

Arthritis research & therapy (2014-03-19)
Masaya Yokota, Kotaro Suzuki, Koji Tokoyoda, Kazuyuki Meguro, Junichi Hosokawa, Shigeru Tanaka, Kei Ikeda, Takashi Mikata, Toshinori Nakayama, Hitoshi Kohsaka, Hiroshi Nakajima
ABSTRACT

In addition to the pivotal roles of mast cells in allergic diseases, recent data suggest that mast cells play crucial roles in a variety of autoimmune responses. However, their roles in the pathogenesis of autoimmune skeletal muscle diseases have not been clarified despite their distribution in skeletal muscle. Therefore, the objective of this study is to determine the roles of mast cells in the development of autoimmune skeletal muscle diseases. The number of mast cells in the affected muscle was examined in patients with dermatomyositis (DM) or polymyositis (PM). The susceptibility of mast cell-deficient WBB6F1-Kit(W)/Kit(Wv) mice (W/W(v) mice) to a murine model of polymyositis, C protein-induced myositis (CIM), was compared with that of wild-type (WT) mice. The effect of mast cell reconstitution with bone marrow-derived mast cells (BMMCs) on the susceptibility of W/W(v) mice to CIM was also evaluated. The number of mast cells in the affected muscle increased in patients with PM as compared with patients with DM. W/W(v) mice exhibited significantly reduced disease incidence and histological scores of CIM as compared with WT mice. The number of CD8⁺ T cells and macrophages in the skeletal muscles of CIM decreased in W/W(v) mice compared with WT mice. Engraftment of BMMCs restored the incidence and histological scores of CIM in W/W(v) mice. Vascular permeability in the skeletal muscle was elevated in WT mice but not in W/W(v) mice upon CIM induction. Mast cells are involved in the pathogenesis of inflammatory myopathy.

MATERIALS
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