Mature Dendritic Cell Suppression by IL-1 Receptor Antagonist on Retinal Pigment Epithelium Cells

Sugita, Sunao; Kawazoe, Yuko; Imai, Ayano; Usui, Yoshihiko; Iwakura, Yoichiro; Isoda, Kikuo; Ito, Masataka; Mochizuki, Manabu

doi:10.1167/iovs.12-11483

Cited by 25 publications

(22 citation statements)

References 42 publications

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“…The finding of RPE immunomodulation has involved isolating and culturing the primary RPE cells that proliferate into a monolayer [5,7]. This is a process that is not usually seen except in wounded retinas.…”

Section: Introductionmentioning

confidence: 99%

Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation

Taylor

Dixit

2015

IJOES

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The eye is an immune privileged tissue with multiple mechanisms of immunosuppression to protect the light gathering tissues from the damage of inflammation. One of theses mechanisms involves retinal pigment epithelial cell suppression of phagosome activation in macrophages. The objective of this work is to determine if the human RPE cell line ARPE-19 is capable of suppressing the activation of the phagolysosome in macrophages in a manner similar to primary RPE. The conditioned media of RPE eyecups, sub-confluent, just confluent cultures, or established confluent cultures of human ARPE-19 cells were generated. These condition media were used to treat macrophages phagocytizing pHrodo bioparticles. After 24 hours incubation the macrophages were imaged by fluorescent microscopy, and fluorescence was measured. The fluorescent intensity is proportional to the amount of bioparticles phagocytized and are in an activated phagolysosome. The conditioned media of in situ mouse RPE eyecups significantly suppressed the activation of phagolysosome. The conditioned media from cultures of human ARPE-19 cells, grown to sub-confluence (50%) or grown to confluence had no effect on phagolysosome activation. In contrast, the conditioned media from established confluent cultures significantly suppressed phagolysosome activation. The neuropeptides alpha-MSH and NPY were depleted from the conditioned media of established confluent ARPE-19 cell cultures. This depleted conditioned media had diminished suppression of phagolysosome activation while promoting macrophage cell death. In addition, the condition media from cultures of ARPE-19 monolayers wounded with a bisecting scrape was diminished in suppressing phagolysosome activation. This technical report suggests that like primary RPE monolayers, established confluent cultures of ARPE-19 cells produce soluble factors that suppress the activation of macrophages, and can be used to study the molecular mechanisms of retinal immunobiology. In addition, the results further demonstrate the importance of an intact monolayer of RPE cells to modulate immune cell activity within the eye.

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Section: Introductionmentioning

confidence: 99%

Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation

Taylor

Dixit

2015

IJOES

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“…Recent studies have shown that ocular resident cells at the inner layer of the blood ocular barrier, such as the iris PE cells, ciliary body PE cells, retinal PE cells, and corneal endothelial cells, have the capacity to suppress the activation of bystander inflammatory immune cells, including the CD4 þ T helper cells. [3][4][5][6][7][8][9][10][11][12] RPE cells are the ocular resident cells that participate in the immune regulation of the posterior segment in the eye. Furthermore, RPE cells have the capacity to convert activated T cells into regulatory T (Treg) cells.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 Recent studies by our own and other various laboratories have investigated the immune regulation by ocular resident cells (i.e., endothelial cells of the cornea and pigment epithelial cells of the iris, ciliary body, and retina). [3][4][5][6][7][8][9][10][11][12][13][14][15] Our research group focused on these ocular resident cells because they are located at the gate of the blood ocular barrier. Based on our current knowledge, it is obvious that immune regulation would work much more efficiently at the gate of the blood ocular barrier as opposed to after the activated CD4 þ T cells enter the eye.…”

mentioning

confidence: 99%

“…Several investigators have previously demonstrated that pigment epithelial (PE) cells of the iris, ciliary body, and retina, as well as the corneal endothelial cells, possess immunoregulatory properties and contribute to the immune privileged site of the eye. [3][4][5][6] For instance, murine RPE cells display immunomodu-latory activity to various immune cells such as: downregulating Th1 cells, 7 Th17 cells, 8 CD8 þ T cells, 9 B cells, 10 macrophages, 11 and dendritic cells 12 ; and upregulating regulatory T cells 13,14 and suppressor myeloid cells. 15 The CD4 þ T cells have identified at least five phenotypes such as Th1 cells, Th2 cells, Th9 cells, Th17 cells, and Th22 cells.…”

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confidence: 99%

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Suppression of IL-22–Producing T Helper 22 Cells by RPE Cells via PD-L1/PD-1 Interactions

Sugita

Kawazoe

Imai

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…Although recent studies have implicated IL-1 receptor (IL-1R) signaling on dendritic cell function, including in the generation of CD8 T cell responses to viruses (22–24), the role of graft- or recipient-derived IL-1R signals in alloimmune T cell responses to organ allografts has not been well investigated. We hypothesized that IL-1R signaling on allograft dendritic cells would be required to provoke optimal donor alloantigen-reactive endogenous memory T cell and de novo T cell responses.…”

Section: Introductionmentioning

confidence: 99%

IL-1 Receptor Signaling on Graft Parenchymal Cells Regulates Memory and De Novo Donor-Reactive CD8 T Cell Responses to Cardiac Allografts

Iida

Tsuda

Tanaka

et al. 2016

The Journal of Immunology

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Reperfusion of organ allografts induces a potent inflammatory response that directs rapid memory T cell, neutrophil and macrophage graft infiltration and their activation to express functions mediating graft tissue injury. The role of cardiac allograft IL-1 receptor signaling in this early inflammation and the downstream primary alloimmune response was investigated. When compared to complete MHC-mismatched wild type cardiac allografts, IL-1R−/− allografts had marked decreases in endogenous memory CD8 T cell and neutrophil infiltration and expression of proinflammatory mediators at early times after transplant whereas endogenous memory CD4 T cell and macrophage infiltration was not decreased. IL-1R−/− allograft recipients also had marked decreases in de novo donor-reactive CD8, but not CD4, T cell development to IFN-γ-producing cells. CD8 T cell-mediated rejection of IL-1R−/− cardiac allografts took 3 weeks longer than wild type allografts. Cardiac allografts from reciprocal bone marrow reconstituted IL-1R−/−/wild type chimeric donors indicated that IL-1R signaling on graft non-hematopoietic-derived, but not bone marrow-derived, cells is required for the potent donor-reactive memory and primary CD8 T cell alloimmune responses observed in response to wild type allografts. These studies implicate IL-1R-mediated signals by allograft parenchymal cells in generating the stimuli provoking development and elicitation of optimal alloimmune responses to the grafts.

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Mature Dendritic Cell Suppression by IL-1 Receptor Antagonist on Retinal Pigment Epithelium Cells

Cited by 25 publications

References 42 publications

Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation

Retinal Pigment Epithelial Cell Line Suppression of Phagolysosome Activation

Suppression of IL-22–Producing T Helper 22 Cells by RPE Cells via PD-L1/PD-1 Interactions

IL-1 Receptor Signaling on Graft Parenchymal Cells Regulates Memory and De Novo Donor-Reactive CD8 T Cell Responses to Cardiac Allografts

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