Japanese journal of ophthalmology · 2011
Suppression of interleukin-17-producing T-helper 17 cells by retinal pigment epithelial cells.
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Sugita Sunao, Horie Shintaro, Yamada Yukiko, Kawazoe Yuko, Takase Hiroshi, Mochizuki Manabu
Аннотация
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.
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.
Предметные рубрики MeSH
AnimalsAutoimmune DiseasesCD4-Positive T-LymphocytesCells, CulturedCoculture TechniquesDisease Models, AnimalEnzyme-Linked Immunosorbent AssayEye ProteinsFlow CytometryImmune ToleranceInterleukin-17Lymphocyte ActivationMiceMice, Inbred C57BLRNA, Small InterferingReal-Time Polymerase Chain ReactionRetinal Pigment EpitheliumRetinol-Binding ProteinsSpleenTh1 CellsTh17 CellsTh2 CellsTransfectionTransforming Growth Factor betaUveitisRetinol-Binding Proteins, Interstitial