Expression of CCR7 and its ligands CCL19/CCL21 in muscles of polymyositis.
Polymyositis is an autoimmune disorder in which autoaggressive CD8(+) T cells are important in the pathogenesis. However, the mechanisms underlying sustained recruitment of these cells in the muscle tissue are still unknown. CCR7 and its ligands CCL19 and CCL21 are a chemokine system related to mononuclear cell migration and antigen presentation, and are suggested to play a key role in several autoimmune disorders. We investigated the expression of CCR7, CCL19 and CCL21 in frozen muscles of polymyositis. In immunohistochemistry, CCR7 was expressed mainly on mononuclear cells that infiltrated in the endomysium of polymyositis. 34.8+/-9.4% of endomysial mononuclear cells expressed CCR7. By double immunostaining, about 60% of endomysial CD8(+) T cells that surrounded the nonnecrotic muscle fibers coexpressed CCR7. Because most endomysial CD8(+) T cells expressed CD45RO, these were regarded as CD45RO(+)CCR7(+)CD8(+) T cells. On the other hand, CCL19 was expressed mainly on muscle fibers in proximity to CCR7(+) mononuclear cells, on the endothelium of the vessels and some mononuclear cells. CCL21 immunoreactivities were found on small numbers of mononuclear cells. In some cases, CCL21 immunoreactivities were also found on muscle fibers and the endothelium of vessels. In RT-PCR analysis, transcripts of CCR7 and CCL21 were detected in all the polymyositis muscles examined and that of CCL19 was detected in five out of seven polymyositis muscles. The CCL19,CCL21/CCR7 chemokine system is expressed in inflamed muscles of polymyositis and may be involved in the pathomechanism of polymyositis.
Tateyama
Maki
M
Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai 980-8574, Japan. mtateyama@em.neurol.med.tohoku.ac.jp
Fujihara
Kazuo
K
Misu
Tatsuro
T
Feng
Juan
J
Onodera
Yoshiaki
Y
Itoyama
Yasuto
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009468:Neuromuscular Diseases / Q000378:metabolism; D017285:Polymyositis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology
C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019707:Receptors, Chemokine