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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)...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9570500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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