Regulation of T-Lymphocyte CCL3 and CCL4 Production by Retinal Pigment Epithelial Cells

Wallace, Carol A.; Moir, Gill; Malone, David F. G.; Duncan, Linda; Devarajan, Gayathri; Crane, Isabel J.

doi:10.1167/iovs.12-10602

Cited by 14 publications

(12 citation statements)

References 45 publications

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“…RPEconditioned medium can differentiate naive T cells to regulatory T (T reg ) cells (61,62). Cocultured RPE can suppress T-cell activation (11) by producing both soluble and membrane-associated immunomodulatory factors (63)(64)(65)(66). Results from our current study show that the ex vivo coculture of RPE with splenic gd T cells directed the differentiation toward regulatory gd T cells that produced suppressive cytokines, such as IL-4 and IL-10 (Fig.…”

Section: Discussionmentioning

confidence: 69%

Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury

et al. 2017

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γδ T cells located near the epithelial barrier are integral components of local inflammatory and innate immune responses. We have previously reported the presence of choroidal γδ T cells in a model of chronic degeneration of the retinal pigment epithelium (RPE). The goals of the current study were to further define the functions of choroidal γδ T cells and to explore the underlying mechanisms of their action. Our data demonstrate that choroidal γδ T cells are activated by RPE injury in response to NaIO treatment, and that they express genes that encode immunosuppressive cytokines, such as IL-4 and IL-10. γδ-T-cell-deficient mice developed profound RPE and retinal damage at doses that caused minimal effects in wild-type mice, and adoptive transfer of γδ T cells prevented sensitization. Intravitreal injection of IL-4 and IL-10 ameliorated RPE toxicity that was induced by NaIO coculture of γδ T cells with RPE explants activated the production of anti-inflammatory cytokines an aryl hydrocarbon receptor (AhR)-dependent mechanism. AhR deficiency abolished the protective effects of γδ T cells after adoptive transfer. Collectively, these findings define important roles for choroid γδ T cells in maintaining tissue homeostasis in the outer retina.-Zhao, Z., Liang, Y., Liu, Y., Xu, P., Flamme-Wiese, M. J., Sun, D., Sun, J., Mullins, R. F., Chen, Y., Cai, J. Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury.

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Section: Discussionmentioning

confidence: 69%

Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury

et al. 2017

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“…It was previously reported that PGE2 mediated the regulatory function of RPE cells in inflammatory T cells through downregulated CCL4. 39 Moreover, the COX2-PGE2 pathways also contribute to the immunoregulatory function of MSCs or regulatory macrophages in modulating other inflammatory diseases. 37,38 On the other hand, however, PGE2 and COX2 were thought to be the The ARPE19 cells were stimulated with different doses of A2E (0, 2, 10, 25 lM) for 6 hours.…”

Section: Discussionmentioning

confidence: 99%

“…[37][38][39] To investigate the mechanisms involved in RPE immunosuppression function in our system, we analyzed PGE2 and COX2 expression in RPE cells by ELISA and Western blot. We found that A2E reduced PGE2 level in RPE cells compared with RPE cells without stimulation (P < 0.01).…”

Section: The A2e Reduced Immunosuppressive Function Of Rpe Cells Thromentioning

confidence: 99%

A2E Suppresses Regulatory Function of RPE Cells in Th1 Cell Differentiation Via Production of IL-1β and Inhibition of PGE2

Shi

Qiu

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Citation: Shi Q, Wang Q, Li J, et al. A2E suppresses regulatory function of RPE cells in Th1 cell differentiation via production of IL-1b and inhibition of PGE2. Invest Ophthalmol Vis Sci. 2015;56:7728-7738. DOI:10.1167/ iovs.15-17677 PURPOSE. Inflammatory status of RPE cells induced by A2E is essential in the development of AMD. Recent research indicated T-cell immunity was involved in the pathological progression of AMD. This study was designed to investigate how A2E suppresses immunoregulatory function of RPE cells in T-cell immunity in vitro. METHODS.Mouse RPE cells or human ARPE19 cells were stimulated with A2E, and co-cultured with naïve T cells under Th1, Th2, Th17, and regulatory T cell (Treg) polarization conditions. The intracellular cytokines or transcript factors of the induced T-cells subset were detected with flow cytometer and qRT-PCR. The ROS levels were detected, and the factors and possible pathways involved in the A2E-laden RPE cells were analyzed through neutralization antibody of IL-1b and inhibitors of related pathways. RESULTS.The A2E reduced regulatory function of RPE cells in Treg differentiation. The A2E-laden RPE cells promoted polarization of Th1 cells in vitro, but not Th2 or Th17 differentiation. The A2E induced RPE cells to release inflammatory cytokines and ROS, but PGE2 production was inhibited. Through neutralization of IL-1b or inhibition of COX2-PGE2 pathways, A2E-laden RPE cells expressed reduced effect in inducing Th1 cells. CONCLUSIONS.The A2E inhibited regulatory function of RPE cells in suppressing Th1 cell immunity in vitro through production of IL-1b and inhibition of PGE2. Our data indicate that A2E could suppress immunoregulatory function of RPE cells and adaptive immunity might play a role in the immune pathogenesis of AMD.

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“…SB431542, which was used to inhibit TGF-β signaling, did not completely block the inhibition of T-cell activation by iPSC-RGCs. In human RPEs, some factors other than TGF-β, such as prostaglandin E2 and soluble CD54, have also been reported to be involved in suppression of T-cell activity [3]. Thus, TGF-β mainly contributes to the T-cell suppression by iPSC-RGCs, but other immunosuppressive molecules other than TGF-β may also contribute.…”

Section: Discussionmentioning

confidence: 99%

“…Retinal ganglion cells (RGCs), which are located in the innermost layer of the retina, are responsible for collecting optical information that reaches the retina, and transmitting it to the brain via the optic nerve [ 1 ]. Retinal pigment epithelial cells (RPEs), which are one of the constituent cells of the retina as well as RGCs, have been reported to possess immune-suppression capacity [ 2 , 3 , 4 , 5 , 6 ]. Stem cell-derived RPE transplantation therapy has already been applied clinically [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells

Edo

Sugita

Futatsugi

et al. 2020

IJMS

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Retinal ganglion cells (RGCs) are impaired in patients such as those with glaucoma and optic neuritis, resulting in permanent vision loss. To restore visual function, development of RGC transplantation therapy is now underway. Induced pluripotent stem cells (iPSCs) are an important source of RGCs for human allogeneic transplantation. We therefore analyzed the immunological characteristics of iPSC-derived RGCs (iPSC-RGCs) to evaluate the possibility of rejection after RGC transplantation. We first assessed the expression of human leukocyte antigen (HLA) molecules on iPSC-RGCs using immunostaining, and then evaluated the effects of iPSC-RGCs to activate lymphocytes using the mixed lymphocyte reaction (MLR) and iPSC-RGC co-cultures. We observed low expression of HLA class I and no expression of HLA class II molecules on iPSC-RGCs. We also found that iPSC-RGCs strongly suppressed various inflammatory immune cells including activated T-cells in the MLR assay and that transforming growth factor-β2 produced by iPSC-RGCs played a critical role in suppression of inflammatory cells in vitro. Our data suggest that iPSC-RGCs have low immunogenicity, and immunosuppressive capacity on lymphocytes. Our study will contribute to predicting immune attacks after RGC transplantation.

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Regulation of T-Lymphocyte CCL3 and CCL4 Production by Retinal Pigment Epithelial Cells

Cited by 14 publications

References 45 publications

Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury

Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury

A2E Suppresses Regulatory Function of RPE Cells in Th1 Cell Differentiation Via Production of IL-1β and Inhibition of PGE2

Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells

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