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      The RPE Cell and the Immune System

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          Abstract

          The RPE cell plays a pivotal role in retinal immunity. In fact, the RPE cell orchestrates both innate and adaptive immunity and contains a plethora of factors to regulate the immune response. Many immunoregulatory activities of the RPE cell are accomplished through cytokine production, toll-like receptor (TLR) activation, complement regulation and antigen presentation. The RPE cells immune regulatory network plays an essential role in retinal immunity and autoimmunity, retinal infections and in a variety of retinal degenerative disorders. Understanding the immune regulatory properties of this cell may provide additional clues to disease mechanisms that may lead to future treatments for many human retinal diseases.

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          Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye.

          P B Medawar (1948)
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            The role of TLR activation in inflammation.

            Moira K. B. Whyte, Matthew Parker, I Sabroe … (2007)
            The Toll-like receptor family was originally identified in Drosophila, where it provides important developmental and immunological signalling. In mammals, the developmental signal appears to have been lost, but the immunological defence role of these receptors has been expanded to provide broad recognition of bacterial, fungal, viral and parasitic pathogens. There is increasing evidence that these receptors go beyond the recognition of microbial molecules to sense host tissue damage. Recognition of host molecules and commensal microbes is also involved in the restoration of normal tissue architecture after injury and in maintenance of epithelial health. Recent developments in the TLR field highlight the importance of these molecules to human health and disease and demonstrate that their targeting, to boost immunity or inhibit inflammation, is both feasible and also potentially challenging. 2007 Pathological Society of Great Britain and Ireland
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              Innate immunity in the retina: Toll-like receptor (TLR) signaling in human retinal pigment epithelial cells

              Matam Kumar, Chandrasekharam Nagineni, Marian Chin … (2004)
              Toll-like receptors (TLRs) are crucial components of innate immunity that participate in host defense against microbial pathogens. We evaluated the expression and function of TLRs in human retinal pigment epithelial (RPE) cells. Real time PCR analysis revealed gene expression for TLRs 1–7, 9, and 10 in RPE cells. TLRs 1 and 3 were the most highly expressed TLRs. Protein expression for TLRs 2, 3, and 4 was observed on RPE cells and this expression was augmented by treatment with poly I:C or interferon-γ (IFN-γ). TLR 3 is the receptor for dsRNA, an intermediate of virus replication. Because RPE cells express TLR 3 and are frequently the site of virus replication within the retina, we evaluated TLR 3 signaling. RPE cells treated with poly I:C produced IFN-β but not IFN-α, and this was inhibited by the treatment of RPE cells with anti-TLR 3 antibody. Human recombinant IFN-β was shown to be biologically active on RPE cells by inhibiting viral replication. Poly I:C treatment of RPE resulted in an increase in the production of IL-6, IL-8, MCP-1, and sICAM-1. The presence of TLRs on RPE cells and the resultant TLR signaling in RPE cells suggest that these molecules may play an important role in innate and adaptive immune responses within the retina.
              Article 0 comments Cited 67 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Alexa Karina Klettner: AlexaKarina.Klettner@uksh.de
                Stefan Dithmar: stefan.dithmar@gmx.de
                Barbara Detrick: bdetrick@jhmi.edu
                John J. Hooks: hooksjohn9@gmail.com
                Journal
                Journal ID (publisher-id): 978-3-030-28384-1
                Journal ID (doi): 10.1007/978-3-030-28384-1
                Journal ID (nlm-ta): Retinal Pigment Epithelium in Health and Disease
                Title: Retinal Pigment Epithelium in Health and Disease
                ISBN (Print): 978-3-030-28383-4
                ISBN (Electronic): 978-3-030-28384-1
                Publication date (Electronic): 31 July 2019
                Pages: 101-114
                Affiliations
                [1 ]GRID grid.9764.c, ISNI 0000 0001 2153 9986, Department of Ophthalmology, , University of Kiel, University Medical Center, ; Kiel, Schleswig-Holstein Germany
                [2 ]GRID grid.5802.f, ISNI 0000 0001 1941 7111, Department of Ophthalmology HSK Wiesbaden, , University of Mainz, ; Wiesbaden, Germany
                [3 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Department of Pathology and Medicine, , School of Medicine, The Johns Hopkins University, ; Baltimore, MD USA
                [4 ]GRID grid.280030.9, ISNI 0000 0001 2150 6316, Laboratory of Immunology, , National Eye Institute, National Institutes of Health, ; Bethesda, MD USA
                Article
                Publisher ID: 6
                DOI: 10.1007/978-3-030-28384-1_6
                PMC ID: 7121222
                SO-VID: 3b665e04-9657-4b3c-9022-d4dfa2cada02
                Copyright © © Springer Nature Switzerland AG 2020
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                Subject: Article
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                issue-copyright-statement © Springer Nature Switzerland AG 2020

                Keywords: innate immunity,adaptive immunity,inflammation,antigen presenting cell,cytokines
                Data availability:
                Keywords: innate immunity, adaptive immunity, inflammation, antigen presenting cell, cytokines

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