miRNA Landscape in Pathogenesis and Treatment of Vogt-Koyanagi-Harada Disease
Date
2021
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Article
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Abstract
miRNAs, one of the members of the noncoding RNA family, are regulators of gene expression in inflammatory and autoimmune diseases. Changes in miRNA pool expression have been associated with differentiation of CD4+ T cells toward an inflammatory phenotype and with loss of self-tolerance in autoimmune diseases. Vogt-Koyanagi-Harada (VKH) disease is a chronic multisystemic pathology, affecting the uvea, inner ear, central nervous system, and skin. Several lines of evidence support an autoimmune etiology for VKH, with loss of tolerance against retinal pigmented epithelium-related self-antigens. This deleterious reaction is characterized by exacerbated inflammation, due to an aberrant T H 1 and T H 17 polarization and secretion of their proinflammatory hallmark cytokines interleukin 6 (IL-6), IL-17, interferon γ, and tumor necrosis factor α, and an impaired CD4+ CD25 high FoxP3+ regulatory T cell function. To restrain inflammation, VKH is pharmacologically treated with corticosteroids and immunosuppressive drugs as first and second line of therapy, respectively. Changes in the expression of miRNAs related to immunoregulatory pathways have been associated with VKH development, whereas some genetic variants of miRNAs have been found to be risk modifiers of VKH. Furthermore, the drugs commonly used in VKH treatment have great influence on miRNA expression, including those miRNAs associated to VKH disease. This relationship between response to therapy and miRNA regulation suggests that these small noncoding molecules might be therapeutic targets for the development of more effective and specific pharmacological therapy for VKH. In this review, we discuss the latest evidence regarding regulation and alteration of miRNA associated with VKH disease and its treatment.
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Citation
Vega-Tapia F, Bustamante M, Valenzuela RA, Urzua CA, Cuitino L. miRNA Landscape in Pathogenesis and Treatment of Vogt-Koyanagi-Harada Disease. Front Cell Dev Biol. 2021 May 10;9:658514. doi: 10.3389/fcell.2021.658514.
Keywords
miRNA, VKH, Autoimmunity, Inflammation, Therapy