miRNA Landscape in Pathogenesis and Treatment of Vogt–Koyanagi–Harada Disease
Journal
Frontiers in Cell and Developmental Biology
ISSN
2296-634X
Date Issued
2021
Author(s)
Fabian Vega-Tapia
Mario Bustamante
Rodrigo A. Valenzuela
Cristhian A. Urzua
Loreto Cuitino
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>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<jats:sup>+</jats:sup> 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<jats:sub><jats:italic>H</jats:italic></jats:sub>1 and T<jats:sub><jats:italic>H</jats:italic></jats:sub>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<jats:sup>+</jats:sup> CD25<jats:sup><jats:italic>high</jats:italic></jats:sup> FoxP3<jats:sup>+</jats:sup> 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.</jats:p>
Subjects
mirna
;
vkh
;
autoimmunity
;
inflammation
;
therapy
;
adalimumab
;
biological product
;
corticosteroid
;
cyclosporine
;
methotrexate
;
microrna
;
microrna 146a
;
microrna 182
;
microrna 20a
;
microrna 23a
;
microrna 301a
;
microrna let 7g 3p
;
mycophenolic acid
;
unclassified drug
;
autoimmunity
;
cd4+ t lymphocyte
;
corticosteroid therapy
;
gene function
;
human
;
immune response
;
immunopathogenesis
;
lymphocyte function
;
nonhuman
;
pharmaceutical care
;
review
;
treatment response
;
vogt koyanagi syndrome