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Suppression of interleukin-17-producing T-helper 17 cells by retinal pigment epithelial cells
Sunao Sugita1, Shintaro Horie2, Yukiko Yamada2
1Department 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.
Purpose:
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.
