T-Cell Suppression by Programmed Cell Death 1 Ligand 1 on Retinal Pigment Epithelium during Inflammatory Conditions

Sugita, Sunao; Usui, Yoshihiko; Horie, Shintaro; Futagami, Yuri; Aburatani, Hiroyuki; Okazaki, Taku; Honjo, Tasuku; Takeuchi, Masaru; Mochizuki, Manabu

doi:10.1167/iovs.08-2846

Cited by 81 publications

(68 citation statements)

References 40 publications

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“…As experimental controls, we used blocking abs against TGF-b, PD-L1 (B7-H1), and cytotoxic T lymphocyte antigen-2a (CTLA-2a) because primary cultured RPE cells produce and secrete these molecules, which are critical mediators of immunosuppression. 12,13,17,18 The mDCs did not produce TNF-a in the presence of RPE cells treated with control abs (TGF-b, CTLA-2a, PD-L1, or isotype control). In contrast, mDCs produced significant amounts of TNF-a if the RPE cells were pretreated with anti-IL-1Ra (Fig.…”

Section: Functional Analysis Of Rpe-dependent Suppression Of Mdcs Viamentioning

confidence: 93%

“…Anti-mouse IL-1Ra neutralizing antibodies (10 lg/mL; R&D Systems) or an isotype control (10 lg/mL; R&D Systems) was used for the RPE-DC assay. As controls, 10 lg/mL of the following abs were used: anti-mouse TGF-b neutralizing antibodies (R&D Systems), anti-mouse CTLA-2a neutralizing antibodies, 17,18 anti-mouse PD-L1 neutralizing antibodies, 13 or isotype rabbit control. After incubation for 2 hours, the abpretreated RPE cells were rinsed once with PBS and added to wells containing the stimulated mDCs.…”

Section: Inhibition Of Dendritic Cells By Rpe Cellsmentioning

confidence: 99%

“…Total RNA in RPE cells was isolated by using TRIzol reagent (Life Technologies) as described previously, 13,27 and in accordance with the manufacturer's instructions. RNA was purified by using a Nucleospin RNA II kit (Macherey Nagel, Inc., Düren, Germany).…”

Section: Genechip Analysismentioning

confidence: 99%

“…Experimental procedures for the GeneChip were performed according to the Affymetrix GeneChip Expression Analysis Technical Manual. 13,27 The cRNA was hybridized to an oligonucleotide microarray (Mouse Genome 430 2.0). The microarray data are deposited in the Gene Expression Omnibus (GEO) public database under accession number GSE5134.…”

Section: Genechip Analysismentioning

confidence: 99%

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

Sugita

Kawazoe

Imai

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To determine whether retinal pigment epithelial (RPE) cells can inhibit mature dendritic cells (mDCs).METHODS. Cultured RPE cells were established from C57BL/6 mice. DCs were established from bone marrow cells of normal mice, and mDCc were induced by culture in medium containing granulocyte macrophage-colony-stimulating factor (GM-CSF) and IL-4 in the presence of lipopolysaccharide and TNF-a. Activation of mDCs was assessed by a proliferation assay and ELISA to measure the production of pro-inflammatory cytokines (TNF-a, IL-1b, and IL-12p40). Expression of major histocompatibility complex (MHC) class II, CD11c, and costimulatory molecules such as CD80, CD86, programmed cell death 1 ligand 1 (PD-L1), and PD-L2 on mDCs or RPE-exposed mDCs was evaluated by immune staining and flow cytometry. Production of IL-1 receptor antagonist (IL-1Ra) by RPE cells was evaluated by oligonucleotide microarray or ELISA. Anti-IL-1Ra neutralizing antibodies or RPE cells from IL-1Ra knockout donors were used for the assay.RESULTS. Cultured RPE cells greatly suppressed the activation of mDCs, especially the production of pro-inflammatory cytokines, and the expression of cell-surface molecules. Moreover, RPE cells significantly suppressed mixed lymphocyte reactions by mDCs. In an examination of immunoregulatory candidate molecules, RPE cells expressed much higher levels of IL-1Ra as compared with control cells, and RPE cells pretreated with recombinant TNF-a and/or IL-1b produced high levels of IL-1Ra. RPE cells in the presence of anti-IL-1Ra antibodies, but not other candidate factors, failed to suppress activation by mDCs. In addition, RPE cells from IL-1Ra null donors failed to suppress mDC activation. CONCLUSIONS.Our results suggest that ocular resident cells can produce pro-inflammatory cytokine antagonist that suppresses antigen-presenting cell activation.

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Section: Functional Analysis Of Rpe-dependent Suppression Of Mdcs Viamentioning

confidence: 93%

Section: Inhibition Of Dendritic Cells By Rpe Cellsmentioning

confidence: 99%

Section: Genechip Analysismentioning

confidence: 99%

Section: Genechip Analysismentioning

confidence: 99%

See 2 more Smart Citations

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

Sugita

Kawazoe

Imai

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…The immunosuppressive properties of these ocular PE cells are summarized in Table 1. Cultured RPE cells suppress T-cell activation by both cell contact and via the secretion of immunosuppressive factors (Ishida et al 2003;Sugita and Streilein 2003;Sugita et al 2006a;Sugita et al 2009). In addition, cultured RPE cells convert both CD4 and CD8 T cells into T regulatory cells in vitro (Sugita et al 2008).…”

Section: Ocular Pigment Epithelial Cellsmentioning

confidence: 99%

Role of ocular pigment epithelial cells in immune privilege

Sugita

2009

Arch. Immunol. Ther. Exp.

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The ocular microenvironment is both immunosuppressive and anti-inflammatory in nature. Pigment epithelial (PE) cells isolated from the eye possess the ability to suppress the T cell receptor-dependent activation of T cells and the induction of regulatory T cells in vitro. This property is dependent on the cells' capacity to produce cell-surface and soluble inhibitory molecules, for example CD86 (B7-2), transforming growth factor (TGF)-beta, thrombospondin-1, programmed cell death 1 ligand 1 (PD-L1/B7-H1), and cytotoxic T lymphocyte-associated antigen 2alpha. Cultured ocular PE cells from the iris, ciliary body, and retina can individually suppress T-cell activation via mechanisms that partially overlap. Moreover, PE-derived regulatory T cells acquire functions that play a role in establishing immune regulation in the eye. Multiple strategies are employed within the eye to control immune-mediated inflammation. This phenomenon is known as immune privilege and is instrumental in helping to prevent extensive damage to bystander cells that would otherwise lead to blindness. This review focuses on the immunosuppressive property and role of ocular PE cells in immune privileged sites.

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PD‐L1 overexpression conveys tolerance of mesenchymal stem cell‐derived cardiomyocyte‐like cells in an allogeneic mouse model

Mardomi

Limoni

Rahbarghazi‬

et al. 2021

Journal Cellular Physiology

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Although the autologously transplanted cells are immunologically durable, allogeneic cell transplantation is inevitable in a series of cases. Mesenchymal stem cells (MSCs) are one of the suitable candidates for cardiac tissue regeneration that have been shown to acquire immunogenicity concurrent with cardiomyogenic differentiation. The present study aimed to exploit PD-L1, as a key immunomodulatory checkpoint ligand to protect the MSCs-derived cardiomyocyte-like cells (CLCs) against the detrimental alloimmunity. Mouse bone marrow-derived MSCs were stably transduced to overexpress PD-L1. MSCs were in vitro differentiated into CLCs and the expressions of immunologic molecules were compared between MSCs and CLCs. The in vitro and in vivo allogeneic immune responses were also examined. The differentiated CLCs had higher expressions of MHC-I and CD80. Upon in vitro coculture with allogeneic splenocytes, CLCs caused more CD4 + and CD8 + T cell activation, lymphocyte proliferation, and interferon-γ (IFN-γ) release in comparison to MSCs. PD-L1 overexpression on CLCs decreased the activation of CD8 + T cells, proliferation of lymphocytes, and release of IFN-γ. The PD-L1-overexpressing CLCs elicited lower in vivo CD4 + and CD8 + T cell activation and reduced the anti-donor antibody response accompanied by increased durability and reduced T cell infiltration. The present study verified the potential of PD-L1 overexpression as a preparative strategy for the protection of allogeneic MSCs-derived CLCs against the detrimental alloreaction.

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T-Cell Suppression by Programmed Cell Death 1 Ligand 1 on Retinal Pigment Epithelium during Inflammatory Conditions

Cited by 81 publications

References 40 publications

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

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

Role of ocular pigment epithelial cells in immune privilege

PD‐L1 overexpression conveys tolerance of mesenchymal stem cell‐derived cardiomyocyte‐like cells in an allogeneic mouse model

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