Inhibitory effect of corneal endothelial cells on IL-17-producing Th17 cells
- Sunao Sugita1,
- Yuko Kawazoe1,
- Yukiko Yamada1,
- Ayano Imai1,
- Shintaro Horie1,
- Satoru Yamagami2,
- Manabu Mochizuki1
- 1Department of Ophthalmology & Visual Science, Tokyo Medical and Dental University Graduate School of Medicine and Dental Sciences, Tokyo, Japan
- 2Corneal Transplantation Section, University of Tokyo Graduate School of Medicine, Tokyo, Japan
- Correspondence to Dr Sunao Sugita, Department of Ophthalmology & Visual Science, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan;
Contributors SS was the principal investigator, who designed and performed the experiments and wrote the manuscript. SY designed and conceptualised the study and drafted and edited the manuscript. YK, YY, AI and SH carried out the experiments (qRT-PCR, flow cytometry and ELISA). MM designed and conceptualised the study and edited the manuscript.
- Accepted 24 October 2011
- Published Online First 17 November 2011
Aim 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.
Conclusion 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.
- Corneal endothelial cells
- T cells
- immune privilege
- experimental and laboratory
- stem cells
- treatment medical
Funding This work was supported by Grants-in-Aid for Scientific Research (C) 20592073 from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
Competing interests None.
Ethics approval The Institutional Animal Research Committee of Tokyo Medical and Dental University approved all the experiments.
Provenance and peer review Not commissioned; externally peer reviewed.