title: Augmented ICOS expression in patients with early diffuse cutaneous systemic sclerosis.
abstract: OBJECTIVE
  Inducible costimulator (ICOS), expressed on activated T cells, and its ligand, ICOS ligand (ICOSL), expressed on antigen-presenting cells, have been considered a single receptor-ligand pair. Here we investigated the expression of ICOS and ICOSL in patients with SSc.
  
  
  METHODS
  ICOS expression on peripheral blood T cells, and ICOSL expression on B cells and macrophages was determined by flow cytometry. Expression of ICOS and ICOSL was assessed by immunohistological staining and real-time PCR of lesional skin.
  
  
  RESULTS
  ICOS expression levels were specifically increased on both peripheral blood memory T cells and Tregs from early dcSSc patients compared with those from healthy controls. Mean ICOSL expression on B cells or macrophages was comparable between SSc patients and healthy controls. ICOS-expressing T cells, ICOSL-expressing macrophages and mRNA levels of ICOS and ICOSL were increased in the lesional skin of patients with early dcSSc. In vitro ICOS costimulation enhanced production of IFN-γ, IL-4 and IL-17A from T cells in SSc patients vs normal controls. Soluble ICOS levels were significantly increased in SSc patients and were negatively associated with the presence of ACAs and positively associated with CRP values. Serum levels of soluble ICOS were more closely associated with clinical features compared with levels of soluble IL-2 receptor.
  
  
  CONCLUSIONS
  Augmented ICOS signalling may contribute to the pathogenesis of SSc during early progressive disease. Soluble ICOS levels may be used as a serum marker for the activity and severity of SSc.
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan. minoruha@derma.m.kanazawa-u.ac.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Hamaguchi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takehara
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000097:blood* / Q000235:genetics; D060889:Inducible T-Cell Co-Stimulator Protein / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D045743:Scleroderma, Diffuse / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D012333:RNA, Messenger