title: Inhibitory effect of corneal endothelial cells on IL-17-producing Th17 cells.
abstract: OBJECTIVE
  To determine whether cultured corneal endothelial (CE) cells suppress interleukin 17 (IL-17)-producing effector T cells in vitro.
  
  
  METHODS
  CE cell lines established from a normal mouse were used. Target bystander T cells were established from normal splenic T cells with anti-CD3 antibodies. Production of IL-17 by target T cells was evaluated by ELISA, flow cytometry and quantitative PCR. To abolish the CE-inhibitory function, transforming growth factor β (TGFβ)-small interfering RNA-transfected CE cells or transwell membrane inserts, which block cell-to-cell contact, were used.
  
  
  RESULTS
  Cultured CE cells greatly suppressed the activation of bystander target cells (pan-T, CD4 T, CD8 T, and B cells) in vitro, particularly inflammatory cytokine production by CD4 cells. Cultured CE cells significantly suppressed IL-17-producing T cells and fully suppressed polarised T helper 17 (Th17) cell lines that are induced by Th17-associated differentiation factors. However, CE cells failed to suppress Th17 cells if the CE cell lines were pretreated with TGFβ small interfering RNA or if direct contact with T cells was blocked with transwell membrane inserts.
  
  
  CONCLUSIONS
  CE cells impair the effector functions and activation of IL-17-producing helper T cells in a cell-contact-dependent mechanism. Thus, corneal endothelium may contribute to the maintenance of the privileged immune status in the eye by inducing peripheral immune tolerance.
authors.affiliation: Department of Ophthalmology & Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. sunaoph@tmd.ac.jp
authors.forename: Sunao
authors.initials: S
authors.lastname: Sugita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawazoe
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Ayano
authors.initials: A
authors.lastname: Imai
authors.forename: Shintaro
authors.initials: S
authors.lastname: Horie
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamagami
authors.forename: Manabu
authors.initials: M
authors.lastname: Mochizuki
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004728:Endothelium, Corneal / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000502:physiology*; D020381:Interleukin-17 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012177:Retinol-Binding Proteins; D058504:Th17 Cells / Q000276:immunology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics; D014605:Uveitis / Q000276:immunology
chemical_list: D020381:Interleukin-17; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D012177:Retinol-Binding Proteins; D016212:Transforming Growth Factor beta