CCR7+ myeloid dendritic cells together with CCR7+ T cells and CCR7+ macrophages invade CCL19+ nonnecrotic muscle fibers in inclusion body myositis.
CCR7 and its ligands CCL19 and CCL21 are a key chemokine system in T cell priming in secondary lymphoid organs, and are rarely expressed in normal muscle tissue. We immunohistochemically investigated the expression of this chemokine system in the muscles of seven patients with inclusion body myositis (IBM). In all cases, CCR7+ mononuclear cells infiltrated in the endomysium, preferentially surrounded and invaded nonnecrotic muscle fibers. Double immunostaining revealed that such CCR7+ mononuclear cells included BDCA-1+ myeloid dendritic cells as well as CD8+ cells, CD4+ cells and CD68+ macrophages. On the other hand, CCL19 was widely expressed on muscle fibers including those invaded by mononuclear cells. CCL19 was also expressed diffusely on endomysial mononuclear cells and endothelium of vessels. Immunoreactivities of CCL21 were detected on some muscle fibers and mononuclear cells. By RT-PCR analyses, mRNA of CCR7 was detected in all the patients and that of CCL19 and CCL21 was detected in six. These findings showed that the CCL19, CCL21/CCR7 chemokine system is expressed in muscles of IBM. The chemokine mediated attraction in dendritic and other immune cells and muscle cells may be crucial in sustained antigen presentation, T cell activation and immune attack to muscles in the pathogenesis of IBM.
Tateyama
Maki
M
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan. mtateyama@em.neurol.med.tohoku.ac.jp
Fujihara
Kazuo
K
Misu
Tatsuro
T
Itoyama
Yasuto
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D018949:Antigens, CD1; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D054415:Chemokine CCL19 / Q000378:metabolism*; D054421:Chemokine CCL21 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006023:Glycoproteins; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000276:immunology* / Q000473:pathology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000276:immunology; D018979:Myositis, Inclusion Body / Q000276:immunology*; D054400:Receptors, CCR7 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D018949:Antigens, CD1; D015214:Antigens, Differentiation, Myelomonocytic; D000954:Antigens, Surface; D015704:CD4 Antigens; D016827:CD8 Antigens; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D006023:Glycoproteins; D054400:Receptors, CCR7; C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; C437944:CD1C protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule