title: CD1a+ survivin+ dendritic cell infiltration in dermal lesions of systemic sclerosis.
abstract: BACKGROUND
  Proto-oncogene survivin is a member of the inhibitor of apoptosis (IAP) family of proteins. The presence of serous antibodies against survivin in patients with systemic sclerosis has been previously reported; however, there are few reports regarding the pathophysiological relationship between survivin and systemic sclerosis. We herein investigated the expression and function of survivin in SSc patients.
  
  
  METHODS
  We performed immunohistochemistry analyses to determine the expression of XIAP, cIAP and survivin in skin lesions from patients with SSc and non-SSc. The expression levels of survivin in peripheral blood mononuclear cells (PBMCs) obtained from SSc patients and healthy controls were evaluated using RT-PCR and flow cytometry. Additionally, the function of survivin was verified with overexpression experiments using monocyte-derived dendritic cells (Mo-DCs).
  
  
  RESULTS
  The expression patterns of both XIAP and cIAP were similar, while only the survivin expression differed between the SSc and non-SSc skin lesions. Survivin-overexpressing cells were detected in the SSc dermis frequently. The positive rate of survivin in SSc dermis (64.3%, 9/14) was higher than that in non-SSc dermis (11.2%, 1/9). Furthermore, survivin+ cells expressed CD1a, one of the DC markers. Real-time PCR and FACS analyses revealed that the survivin-WT (wild type) expression levels in PBMCs, in particular CD14+ monocytes, from SSc patients were higher than that from healthy controls. Additionally, the overexpression experiments showed that survivin-WT-overexpressing CD1a+ Mo-DCs have the characteristics of promoting cell cycle progression and decreasing apoptotic cells.
  
  
  CONCLUSIONS
  These findings suggest that dermal survivin+ CD1a+ cell infiltration may be a potential biomarker of SSc skin lesions. PBMCs and monocytes from SSc patients also overexpressed survivin; therefore, dermal survivin+ DC may be derived from peripheral blood monocytes. Additionally, survivin may be involved in dermal CD1a+ DC proliferation through cell cycle activation and resistance to apoptosis. Survivin may be an important molecule for the pathogenesis of SSc.
authors.affiliation: Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. sho-mokuda@hiroshima-u.ac.jp.|Department of Pathology, Ehime University Proteo-Science Centre and Graduate School of Medicine, Shizukawa, Toon, Ehime, 791-0295, Japan. sho-mokuda@hiroshima-u.ac.jp.|Department of Internal Medicine, Center for Rheumatic Diseases, Dohgo Spa Hospital, 21-21 Otsu Dohgo-Himezuka, Matsuyama, Ehime, 790-0858, Japan. sho-mokuda@hiroshima-u.ac.jp.|Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. sho-mokuda@hiroshima-u.ac.jp.
authors.forename: Sho
authors.initials: S
authors.lastname: Mokuda
authors.affiliation: Department of Pathology, Ehime University Proteo-Science Centre and Graduate School of Medicine, Shizukawa, Toon, Ehime, 791-0295, Japan. tats_m@gifu-u.ac.jp.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Nephrology Center and the Okinaka Memorial Institute for Medical Research, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan. ubara@toranomon.gr.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ubara
authors.affiliation: Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. mkanno@hiroshima-u.ac.jp.
authors.forename: Masamoto
authors.initials: M
authors.lastname: Kanno
authors.affiliation: Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. esugiyam@hiroshima-u.ac.jp.
authors.forename: Eiji
authors.initials: E
authors.lastname: Sugiyama
authors.affiliation: Department of Internal Medicine, Center for Rheumatic Diseases, Dohgo Spa Hospital, 21-21 Otsu Dohgo-Himezuka, Matsuyama, Ehime, 790-0858, Japan. keetakas@ehime.med.or.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takasugi
authors.affiliation: Department of Pathology, Ehime University Proteo-Science Centre and Graduate School of Medicine, Shizukawa, Toon, Ehime, 791-0295, Japan. masumoto@m.ehime-u.ac.jp.
authors.forename: Junya
authors.initials: J
authors.lastname: Masumoto
mesh_terms: D000328:Adult; D000368:Aged; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D020405:Dermis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000378:metabolism; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; C107489:BIRC5 protein, human; C419393:CD1a antigen; D051034:Inhibitor of Apoptosis Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human