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Replenishing decoy extracellular vesicles inhibits phenotype remodeling of tissue-resident cells in inflammation-driven arthritis

The interleukin 6 (IL6) signaling pathway plays pleiotropic roles in regulating the inflammatory milieu that contributes to arthritis development. Here, we show that activation of IL6 trans-signaling induces phenotypic transitions in tissue-resident cells toward an inflammatory state. The establishm...

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Autores principales: Liang, Mengmeng, Wang, Ke, Wei, Xiaoyu, Gong, Xiaoshan, Tang, Hao, Xue, Hao, Wang, Jing, Yin, Pengbin, Zhang, Licheng, Ma, Zaisong, Dou, Ce, Dong, Shiwu, Xu, Jianzhong, Luo, Fei, Ma, Qinyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591050/
https://www.ncbi.nlm.nih.gov/pubmed/37852176
http://dx.doi.org/10.1016/j.xcrm.2023.101228
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author Liang, Mengmeng
Wang, Ke
Wei, Xiaoyu
Gong, Xiaoshan
Tang, Hao
Xue, Hao
Wang, Jing
Yin, Pengbin
Zhang, Licheng
Ma, Zaisong
Dou, Ce
Dong, Shiwu
Xu, Jianzhong
Luo, Fei
Ma, Qinyu
author_facet Liang, Mengmeng
Wang, Ke
Wei, Xiaoyu
Gong, Xiaoshan
Tang, Hao
Xue, Hao
Wang, Jing
Yin, Pengbin
Zhang, Licheng
Ma, Zaisong
Dou, Ce
Dong, Shiwu
Xu, Jianzhong
Luo, Fei
Ma, Qinyu
author_sort Liang, Mengmeng
collection PubMed
description The interleukin 6 (IL6) signaling pathway plays pleiotropic roles in regulating the inflammatory milieu that contributes to arthritis development. Here, we show that activation of IL6 trans-signaling induces phenotypic transitions in tissue-resident cells toward an inflammatory state. The establishment of arthritis increases the serum number of extracellular vesicles (EVs), while these EVs express more IL6 signal transducer (IL6ST, also known as gp130) on their surface. Transferring these EVs can block IL6 trans-signaling in vitro by acting as decoys that trap hyper IL6 and prevent inflammatory amplification in recipient arthritic mice. By genetically fusing EV-sorting domains with extracellular domains of receptors, we engineered EVs that harbor a higher quantity of signaling-incompetent decoy receptors. These exogenous decoy EVs exhibit significant potential in eliciting efficient anti-inflammatory effects in vivo. Our findings suggest an inherent resistance of decoy EVs against inflammation, highlighting the therapeutic potential of efficient decoy EVs in treating inflammatory diseases.
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spelling pubmed-105910502023-10-24 Replenishing decoy extracellular vesicles inhibits phenotype remodeling of tissue-resident cells in inflammation-driven arthritis Liang, Mengmeng Wang, Ke Wei, Xiaoyu Gong, Xiaoshan Tang, Hao Xue, Hao Wang, Jing Yin, Pengbin Zhang, Licheng Ma, Zaisong Dou, Ce Dong, Shiwu Xu, Jianzhong Luo, Fei Ma, Qinyu Cell Rep Med Article The interleukin 6 (IL6) signaling pathway plays pleiotropic roles in regulating the inflammatory milieu that contributes to arthritis development. Here, we show that activation of IL6 trans-signaling induces phenotypic transitions in tissue-resident cells toward an inflammatory state. The establishment of arthritis increases the serum number of extracellular vesicles (EVs), while these EVs express more IL6 signal transducer (IL6ST, also known as gp130) on their surface. Transferring these EVs can block IL6 trans-signaling in vitro by acting as decoys that trap hyper IL6 and prevent inflammatory amplification in recipient arthritic mice. By genetically fusing EV-sorting domains with extracellular domains of receptors, we engineered EVs that harbor a higher quantity of signaling-incompetent decoy receptors. These exogenous decoy EVs exhibit significant potential in eliciting efficient anti-inflammatory effects in vivo. Our findings suggest an inherent resistance of decoy EVs against inflammation, highlighting the therapeutic potential of efficient decoy EVs in treating inflammatory diseases. Elsevier 2023-10-17 /pmc/articles/PMC10591050/ /pubmed/37852176 http://dx.doi.org/10.1016/j.xcrm.2023.101228 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Liang, Mengmeng
Wang, Ke
Wei, Xiaoyu
Gong, Xiaoshan
Tang, Hao
Xue, Hao
Wang, Jing
Yin, Pengbin
Zhang, Licheng
Ma, Zaisong
Dou, Ce
Dong, Shiwu
Xu, Jianzhong
Luo, Fei
Ma, Qinyu
Replenishing decoy extracellular vesicles inhibits phenotype remodeling of tissue-resident cells in inflammation-driven arthritis
title Replenishing decoy extracellular vesicles inhibits phenotype remodeling of tissue-resident cells in inflammation-driven arthritis
title_full Replenishing decoy extracellular vesicles inhibits phenotype remodeling of tissue-resident cells in inflammation-driven arthritis
title_fullStr Replenishing decoy extracellular vesicles inhibits phenotype remodeling of tissue-resident cells in inflammation-driven arthritis
title_full_unstemmed Replenishing decoy extracellular vesicles inhibits phenotype remodeling of tissue-resident cells in inflammation-driven arthritis
title_short Replenishing decoy extracellular vesicles inhibits phenotype remodeling of tissue-resident cells in inflammation-driven arthritis
title_sort replenishing decoy extracellular vesicles inhibits phenotype remodeling of tissue-resident cells in inflammation-driven arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591050/
https://www.ncbi.nlm.nih.gov/pubmed/37852176
http://dx.doi.org/10.1016/j.xcrm.2023.101228
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