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IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish
MyD88 is a conserved intracellular adaptor, which plays an important role in the innate immune system. MyD88 transmits signals for downstream of toll-like and IL-1 receptors to activate NF-κB signaling pathway, which is tightly controlled in the immune response to maintain immune intensity and immun...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179762/ https://www.ncbi.nlm.nih.gov/pubmed/32373114 http://dx.doi.org/10.3389/fimmu.2020.00606 |
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author | Yan, Xiaolong Zhao, Xueyan Huo, Ruixuan Xu, Tianjun |
author_facet | Yan, Xiaolong Zhao, Xueyan Huo, Ruixuan Xu, Tianjun |
author_sort | Yan, Xiaolong |
collection | PubMed |
description | MyD88 is a conserved intracellular adaptor, which plays an important role in the innate immune system. MyD88 transmits signals for downstream of toll-like and IL-1 receptors to activate NF-κB signaling pathway, which is tightly controlled in the immune response to maintain immune intensity and immune homeostasis at different stages. NF-κB signaling pathway has been extensively studied in mammals, but regulatory molecular mechanism is still unclear in teleost fish. We determined that IRF3 and IRF8 can regulate MyD88-mediated NF-κB signaling pathway in fish. Interestingly, MyD88 is precisely regulated by IRF3 and IRF8 through the same mechanism but in completely opposite ways. IRF3 promotes MyD88-mediated NF-κB signaling pathway, whereas IRF8 inhibits the signaling pathway. MyD88 is regulated via ubiquitin–proteasome degradation, whereas IRF3 or IRF8 inhibited or promoted MyD88 degradation in this pathway. Specifically, in the early stage of lipopolysaccharide (LPS) stimulation or Vibrio infection, up-regulation of IRF3 and down-regulation of IRF8 eventually increased MyD88 expression to activate the NF-κB signaling pathway to trigger immune response. In the late stage of stimulation, down-regulated IRF3 and up-regulated IRF8 synergistically regulate the expression of MyD88 to a normal level, thus maintaining the immune balance of homeostasis and preventing serious damage from persistent over-immunization. This study presents information on Myd88–NF-κB signaling pathway in teleost fish and provides new insights into its regulatory mechanism in fish immune system. |
format | Online Article Text |
id | pubmed-7179762 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71797622020-05-05 IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish Yan, Xiaolong Zhao, Xueyan Huo, Ruixuan Xu, Tianjun Front Immunol Immunology MyD88 is a conserved intracellular adaptor, which plays an important role in the innate immune system. MyD88 transmits signals for downstream of toll-like and IL-1 receptors to activate NF-κB signaling pathway, which is tightly controlled in the immune response to maintain immune intensity and immune homeostasis at different stages. NF-κB signaling pathway has been extensively studied in mammals, but regulatory molecular mechanism is still unclear in teleost fish. We determined that IRF3 and IRF8 can regulate MyD88-mediated NF-κB signaling pathway in fish. Interestingly, MyD88 is precisely regulated by IRF3 and IRF8 through the same mechanism but in completely opposite ways. IRF3 promotes MyD88-mediated NF-κB signaling pathway, whereas IRF8 inhibits the signaling pathway. MyD88 is regulated via ubiquitin–proteasome degradation, whereas IRF3 or IRF8 inhibited or promoted MyD88 degradation in this pathway. Specifically, in the early stage of lipopolysaccharide (LPS) stimulation or Vibrio infection, up-regulation of IRF3 and down-regulation of IRF8 eventually increased MyD88 expression to activate the NF-κB signaling pathway to trigger immune response. In the late stage of stimulation, down-regulated IRF3 and up-regulated IRF8 synergistically regulate the expression of MyD88 to a normal level, thus maintaining the immune balance of homeostasis and preventing serious damage from persistent over-immunization. This study presents information on Myd88–NF-κB signaling pathway in teleost fish and provides new insights into its regulatory mechanism in fish immune system. Frontiers Media S.A. 2020-04-16 /pmc/articles/PMC7179762/ /pubmed/32373114 http://dx.doi.org/10.3389/fimmu.2020.00606 Text en Copyright © 2020 Yan, Zhao, Huo and Xu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Yan, Xiaolong Zhao, Xueyan Huo, Ruixuan Xu, Tianjun IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish |
title | IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish |
title_full | IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish |
title_fullStr | IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish |
title_full_unstemmed | IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish |
title_short | IRF3 and IRF8 Regulate NF-κB Signaling by Targeting MyD88 in Teleost Fish |
title_sort | irf3 and irf8 regulate nf-κb signaling by targeting myd88 in teleost fish |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179762/ https://www.ncbi.nlm.nih.gov/pubmed/32373114 http://dx.doi.org/10.3389/fimmu.2020.00606 |
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