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Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms

IL-24 is a multifunctional cytokine that regulates both immune cells and epithelial cells. Although its elevation is associated with a number of autoimmune diseases, its tolerogenic properties against autoreactive T cells have recently been revealed in an animal model of central nervous system (CNS)...

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Detalles Bibliográficos
Autores principales: Zhang, Xuan, Hu, Cuiping, Zhong, Yajie, Qiao, Dijie, Chi, Wei, Shen, Huangxuan, Chong, Waipo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570500/
https://www.ncbi.nlm.nih.gov/pubmed/36233291
http://dx.doi.org/10.3390/ijms231911988
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author Zhang, Xuan
Hu, Cuiping
Zhong, Yajie
Qiao, Dijie
Chi, Wei
Shen, Huangxuan
Chong, Waipo
author_facet Zhang, Xuan
Hu, Cuiping
Zhong, Yajie
Qiao, Dijie
Chi, Wei
Shen, Huangxuan
Chong, Waipo
author_sort Zhang, Xuan
collection PubMed
description IL-24 is a multifunctional cytokine that regulates both immune cells and epithelial cells. Although its elevation is associated with a number of autoimmune diseases, its tolerogenic properties against autoreactive T cells have recently been revealed in an animal model of central nervous system (CNS) autoimmunity by inhibiting the pathogenic Th17 response. To explore the potential of IL-24 as a therapeutic agent in CNS autoimmunity, we induced experimental autoimmune uveitis (EAU) in wildtype mice and intravitreally injected IL-24 into the inflamed eye after disease onset. We found that the progression of ocular inflammation was significantly inhibited in the IL-24-treated eye when compared to the control eye. More importantly, IL-24 treatment suppressed cytokine production from ocular-infiltrating, pathogenic Th1 and Th17 cells. In vitro experiments confirmed that IL-24 suppressed both Th1 and Th17 differentiation by regulating their master transcription factors T-bet and RORγt, respectively. In addition, we found that intravitreal injection of IL-24 suppressed the production of proinflammatory cytokines and chemokines from the retinas of the EAU-inflamed eyes. This observation appears to be applicable in humans, as IL-24 similarly inhibits human retinal pigment epithelium cells ARPE-19. In conclusion, we report here that IL-24, as a multifunctional cytokine, is capable of resolving ocular inflammation in EAU mice by targeting both uveitogenic T cells and RPE cells. This study sheds new light on IL-24 as a potential therapeutic candidate for autoimmune uveitis.
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spelling pubmed-95705002022-10-17 Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms Zhang, Xuan Hu, Cuiping Zhong, Yajie Qiao, Dijie Chi, Wei Shen, Huangxuan Chong, Waipo Int J Mol Sci Article IL-24 is a multifunctional cytokine that regulates both immune cells and epithelial cells. Although its elevation is associated with a number of autoimmune diseases, its tolerogenic properties against autoreactive T cells have recently been revealed in an animal model of central nervous system (CNS) autoimmunity by inhibiting the pathogenic Th17 response. To explore the potential of IL-24 as a therapeutic agent in CNS autoimmunity, we induced experimental autoimmune uveitis (EAU) in wildtype mice and intravitreally injected IL-24 into the inflamed eye after disease onset. We found that the progression of ocular inflammation was significantly inhibited in the IL-24-treated eye when compared to the control eye. More importantly, IL-24 treatment suppressed cytokine production from ocular-infiltrating, pathogenic Th1 and Th17 cells. In vitro experiments confirmed that IL-24 suppressed both Th1 and Th17 differentiation by regulating their master transcription factors T-bet and RORγt, respectively. In addition, we found that intravitreal injection of IL-24 suppressed the production of proinflammatory cytokines and chemokines from the retinas of the EAU-inflamed eyes. This observation appears to be applicable in humans, as IL-24 similarly inhibits human retinal pigment epithelium cells ARPE-19. In conclusion, we report here that IL-24, as a multifunctional cytokine, is capable of resolving ocular inflammation in EAU mice by targeting both uveitogenic T cells and RPE cells. This study sheds new light on IL-24 as a potential therapeutic candidate for autoimmune uveitis. MDPI 2022-10-09 /pmc/articles/PMC9570500/ /pubmed/36233291 http://dx.doi.org/10.3390/ijms231911988 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Xuan
Hu, Cuiping
Zhong, Yajie
Qiao, Dijie
Chi, Wei
Shen, Huangxuan
Chong, Waipo
Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms
title Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms
title_full Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms
title_fullStr Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms
title_full_unstemmed Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms
title_short Multifunctional Interleukin-24 Resolves Neuroretina Autoimmunity via Diverse Mechanisms
title_sort multifunctional interleukin-24 resolves neuroretina autoimmunity via diverse mechanisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570500/
https://www.ncbi.nlm.nih.gov/pubmed/36233291
http://dx.doi.org/10.3390/ijms231911988
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