title: Suppression of interleukin-17-producing T-helper 17 cells by retinal pigment epithelial cells.
abstract: OBJECTIVE
  To determine whether retinal pigment epithelial (RPE) cells can inhibit cytokine production by activated T helper (Th) cells.
  
  
  METHODS
  Primary RPE cells were cultured from normal C57BL/6 mice. Target bystander T cells were established from normal splenic T cells with anti-CD3 antibodies. T-cell activation was assessed for production of cytokines, determined by ELISA. Production of IL-17 on target T cells was evaluated using oligonucleotide microarray, RT-PCR and flow cytometry. TGFβ small interfering RNA was used to inhibit the RPE cells' inhibitory function.
  
  
  RESULTS
  The cultured RPE cells greatly suppressed the activation of bystander CD4(+) T cells in vitro, especially cytokine production by target T helper cells (Th1 cells, Th2 cells and Th17 cells, but not Th3 cells). The cultured RPE cells and RPE supernatants significantly suppressed the IL-17-producing CD4(+) T cells and fully suppressed the polarized Th17 cell lines that were induced by recombinant proteins IL-6 and TGFβ2. However, the RPE cells failed to suppress the IL-17-producing T cells in the presence of rIL-6. In addition, the TGFβ produced by the RPE cells suppressed the Th17 cells.
  
  
  CONCLUSIONS
  These results indicate that RPE cells have an immunosuppressive effect on Th17-type effector T cells, which highlights a role for ocular resident cells in establishing immune regulation in the eye.
authors.affiliation: Department of Ophthalmology and 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.affiliation: Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Horie
authors.affiliation: Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawazoe
authors.affiliation: Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takase
authors.affiliation: Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
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; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000502:physiology*; D020381:Interleukin-17 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055213:Retinal Pigment Epithelium / Q000276:immunology*; D012177:Retinol-Binding Proteins; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics; D014605:Uveitis / Q000276:immunology; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D005136:Eye Proteins; D020381:Interleukin-17; D034741:RNA, Small Interfering; D012177:Retinol-Binding Proteins; D016212:Transforming Growth Factor beta; D000099214:Retinol-Binding Proteins, Interstitial