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Suppression of interleukin-17-producing T-helper 17 cells by retinal pigment epithelial cells

  • Laboratory Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgments

We would like to thank Mrs. Ikuyo Yamamoto for her expert technical assistance. This work was supported by Scientific Research (C) 20592073 and Grants-in-Aid for Young Scientists (B) 21791671 and 21791672 of the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Correspondence to Sunao Sugita.

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Sugita, S., Horie, S., Yamada, Y. et al. Suppression of interleukin-17-producing T-helper 17 cells by retinal pigment epithelial cells. Jpn J Ophthalmol 55, 565–575 (2011). https://doi.org/10.1007/s10384-011-0064-9

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  • DOI: https://doi.org/10.1007/s10384-011-0064-9

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