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Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk
Epidermal infiltration of neutrophils is a hallmark of psoriasis, where their activation leads to release of neutrophil extracellular traps (NETs). The contribution of NETs to psoriasis pathogenesis has been unclear, but here we demonstrate that NETs drive inflammatory responses in skin through acti...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460719/ https://www.ncbi.nlm.nih.gov/pubmed/31024570 http://dx.doi.org/10.3389/fimmu.2019.00746 |
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author | Shao, Shuai Fang, Hui Dang, Erle Xue, Ke Zhang, Jieyu Li, Bing Qiao, Hongjiang Cao, Tianyu Zhuang, Yuchen Shen, Shengxian Zhang, Tongmei Qiao, Pei Li, Caixia Gudjonsson, Johann E. Wang, Gang |
author_facet | Shao, Shuai Fang, Hui Dang, Erle Xue, Ke Zhang, Jieyu Li, Bing Qiao, Hongjiang Cao, Tianyu Zhuang, Yuchen Shen, Shengxian Zhang, Tongmei Qiao, Pei Li, Caixia Gudjonsson, Johann E. Wang, Gang |
author_sort | Shao, Shuai |
collection | PubMed |
description | Epidermal infiltration of neutrophils is a hallmark of psoriasis, where their activation leads to release of neutrophil extracellular traps (NETs). The contribution of NETs to psoriasis pathogenesis has been unclear, but here we demonstrate that NETs drive inflammatory responses in skin through activation of epidermal TLR4/IL-36R crosstalk. This activation is dependent upon NETs formation and integrity, as targeting NETs with DNase I or CI-amidine in vivo improves disease in the imiquimod (IMQ)-induced psoriasis-like mouse model, decreasing IL-17A, lipocalin2 (LCN2), and IL-36G expression. Proinflammatory activity of NETs, and LCN2 induction, is dependent upon activation of TLR4/IL-36R crosstalk and MyD88/nuclear factor-kappa B (NF-κB) down-stream signaling, but independent of TLR7 or TLR9. Notably, both TLR4 inhibition and LCN2 neutralization alleviate psoriasis-like inflammation and NETs formation in both the IMQ model and K14-VEGF transgenic mice. In summary, these results outline the mechanisms for the proinflammatory activity of NETs in skin and identify NETs/TLR4 as novel therapeutic targets in psoriasis. |
format | Online Article Text |
id | pubmed-6460719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64607192019-04-25 Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk Shao, Shuai Fang, Hui Dang, Erle Xue, Ke Zhang, Jieyu Li, Bing Qiao, Hongjiang Cao, Tianyu Zhuang, Yuchen Shen, Shengxian Zhang, Tongmei Qiao, Pei Li, Caixia Gudjonsson, Johann E. Wang, Gang Front Immunol Immunology Epidermal infiltration of neutrophils is a hallmark of psoriasis, where their activation leads to release of neutrophil extracellular traps (NETs). The contribution of NETs to psoriasis pathogenesis has been unclear, but here we demonstrate that NETs drive inflammatory responses in skin through activation of epidermal TLR4/IL-36R crosstalk. This activation is dependent upon NETs formation and integrity, as targeting NETs with DNase I or CI-amidine in vivo improves disease in the imiquimod (IMQ)-induced psoriasis-like mouse model, decreasing IL-17A, lipocalin2 (LCN2), and IL-36G expression. Proinflammatory activity of NETs, and LCN2 induction, is dependent upon activation of TLR4/IL-36R crosstalk and MyD88/nuclear factor-kappa B (NF-κB) down-stream signaling, but independent of TLR7 or TLR9. Notably, both TLR4 inhibition and LCN2 neutralization alleviate psoriasis-like inflammation and NETs formation in both the IMQ model and K14-VEGF transgenic mice. In summary, these results outline the mechanisms for the proinflammatory activity of NETs in skin and identify NETs/TLR4 as novel therapeutic targets in psoriasis. Frontiers Media S.A. 2019-04-05 /pmc/articles/PMC6460719/ /pubmed/31024570 http://dx.doi.org/10.3389/fimmu.2019.00746 Text en Copyright © 2019 Shao, Fang, Dang, Xue, Zhang, Li, Qiao, Cao, Zhuang, Shen, Zhang, Qiao, Li, Gudjonsson and Wang. 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 Shao, Shuai Fang, Hui Dang, Erle Xue, Ke Zhang, Jieyu Li, Bing Qiao, Hongjiang Cao, Tianyu Zhuang, Yuchen Shen, Shengxian Zhang, Tongmei Qiao, Pei Li, Caixia Gudjonsson, Johann E. Wang, Gang Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk |
title | Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk |
title_full | Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk |
title_fullStr | Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk |
title_full_unstemmed | Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk |
title_short | Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk |
title_sort | neutrophil extracellular traps promote inflammatory responses in psoriasis via activating epidermal tlr4/il-36r crosstalk |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460719/ https://www.ncbi.nlm.nih.gov/pubmed/31024570 http://dx.doi.org/10.3389/fimmu.2019.00746 |
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