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An IL-17-EGFR-TRAF4 axis contributes to the alleviation of lung inflammation in severe influenza
Excessive inflammation is a postulated cause of severe disease and death in respiratory virus infections. In response to severe influenza virus infection, adoptively transferred naïve hemagglutinin-specific CD4(+) T cells from CD4(+) TCR-transgenic 6.5 mice drive an IFN-γ-producing Th1 response in w...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239044/ https://www.ncbi.nlm.nih.gov/pubmed/37270623 http://dx.doi.org/10.1038/s42003-023-04982-0 |
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author | Dutta, Avijit Hung, Chen-Yiu Chen, Tse-Ching Hsiao, Sung-Han Chang, Chia-Shiang Lin, Yung-Chang Lin, Chun-Yen Huang, Ching-Tai |
author_facet | Dutta, Avijit Hung, Chen-Yiu Chen, Tse-Ching Hsiao, Sung-Han Chang, Chia-Shiang Lin, Yung-Chang Lin, Chun-Yen Huang, Ching-Tai |
author_sort | Dutta, Avijit |
collection | PubMed |
description | Excessive inflammation is a postulated cause of severe disease and death in respiratory virus infections. In response to severe influenza virus infection, adoptively transferred naïve hemagglutinin-specific CD4(+) T cells from CD4(+) TCR-transgenic 6.5 mice drive an IFN-γ-producing Th1 response in wild-type mice. It helps in virus clearance but also causes collateral damage and disease aggravation. The donor 6.5 mice have all the CD4(+) T cells with TCR specificity toward influenza hemagglutinin. Still, the infected 6.5 mice do not suffer from robust inflammation and grave outcome. The initial Th1 response wanes with time, and a prominent Th17 response of recent thymic emigrants alleviates inflammation and bestows protection in 6.5 mice. Our results suggest that viral neuraminidase-activated TGF-β of the Th1 cells guides the Th17 evolution, and IL-17 signaling through the non-canonical IL-17 receptor EGFR activates the scaffold protein TRAF4 more than TRAF6 during alleviation of lung inflammation in severe influenza. |
format | Online Article Text |
id | pubmed-10239044 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102390442023-06-05 An IL-17-EGFR-TRAF4 axis contributes to the alleviation of lung inflammation in severe influenza Dutta, Avijit Hung, Chen-Yiu Chen, Tse-Ching Hsiao, Sung-Han Chang, Chia-Shiang Lin, Yung-Chang Lin, Chun-Yen Huang, Ching-Tai Commun Biol Article Excessive inflammation is a postulated cause of severe disease and death in respiratory virus infections. In response to severe influenza virus infection, adoptively transferred naïve hemagglutinin-specific CD4(+) T cells from CD4(+) TCR-transgenic 6.5 mice drive an IFN-γ-producing Th1 response in wild-type mice. It helps in virus clearance but also causes collateral damage and disease aggravation. The donor 6.5 mice have all the CD4(+) T cells with TCR specificity toward influenza hemagglutinin. Still, the infected 6.5 mice do not suffer from robust inflammation and grave outcome. The initial Th1 response wanes with time, and a prominent Th17 response of recent thymic emigrants alleviates inflammation and bestows protection in 6.5 mice. Our results suggest that viral neuraminidase-activated TGF-β of the Th1 cells guides the Th17 evolution, and IL-17 signaling through the non-canonical IL-17 receptor EGFR activates the scaffold protein TRAF4 more than TRAF6 during alleviation of lung inflammation in severe influenza. Nature Publishing Group UK 2023-06-03 /pmc/articles/PMC10239044/ /pubmed/37270623 http://dx.doi.org/10.1038/s42003-023-04982-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Dutta, Avijit Hung, Chen-Yiu Chen, Tse-Ching Hsiao, Sung-Han Chang, Chia-Shiang Lin, Yung-Chang Lin, Chun-Yen Huang, Ching-Tai An IL-17-EGFR-TRAF4 axis contributes to the alleviation of lung inflammation in severe influenza |
title | An IL-17-EGFR-TRAF4 axis contributes to the alleviation of lung inflammation in severe influenza |
title_full | An IL-17-EGFR-TRAF4 axis contributes to the alleviation of lung inflammation in severe influenza |
title_fullStr | An IL-17-EGFR-TRAF4 axis contributes to the alleviation of lung inflammation in severe influenza |
title_full_unstemmed | An IL-17-EGFR-TRAF4 axis contributes to the alleviation of lung inflammation in severe influenza |
title_short | An IL-17-EGFR-TRAF4 axis contributes to the alleviation of lung inflammation in severe influenza |
title_sort | il-17-egfr-traf4 axis contributes to the alleviation of lung inflammation in severe influenza |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239044/ https://www.ncbi.nlm.nih.gov/pubmed/37270623 http://dx.doi.org/10.1038/s42003-023-04982-0 |
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