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Vagus nerve plays a pivotal role in CD4+ T cell differentiation during CVB3-induced murine acute myocarditis

Abnormalities in CD4(+) T cell (Th cell) differentiation play an important role in the pathogenesis of viral myocarditis (VMC). Our previous studies demonstrated that activation of the cholinergic anti-inflammatory pathway (CAP) alleviated the inflammatory response. In addition, we observed that rig...

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Autores principales: Yue-Chun, Li, Gu, Xiao-Hong, Li-Sha, Ge, Zhou, De-Pu, Xing, Chao, Guo, Xiao-Ling, Pan, Lu-Lu, Song, Shi-Yang, Yu, Li-Li, Chen, Guang-Yi, Lin, Jia-Feng, Chu, Mao-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834089/
https://www.ncbi.nlm.nih.gov/pubmed/33380272
http://dx.doi.org/10.1080/21505594.2020.1869384
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author Yue-Chun, Li
Gu, Xiao-Hong
Li-Sha, Ge
Zhou, De-Pu
Xing, Chao
Guo, Xiao-Ling
Pan, Lu-Lu
Song, Shi-Yang
Yu, Li-Li
Chen, Guang-Yi
Lin, Jia-Feng
Chu, Mao-Ping
author_facet Yue-Chun, Li
Gu, Xiao-Hong
Li-Sha, Ge
Zhou, De-Pu
Xing, Chao
Guo, Xiao-Ling
Pan, Lu-Lu
Song, Shi-Yang
Yu, Li-Li
Chen, Guang-Yi
Lin, Jia-Feng
Chu, Mao-Ping
author_sort Yue-Chun, Li
collection PubMed
description Abnormalities in CD4(+) T cell (Th cell) differentiation play an important role in the pathogenesis of viral myocarditis (VMC). Our previous studies demonstrated that activation of the cholinergic anti-inflammatory pathway (CAP) alleviated the inflammatory response. In addition, we observed that right cervical vagotomy aggravates VMC by inhibiting CAP. However, the vagus nerve’s effect on differentiation of CD4(+) T cells has not been studied in VMC mice to date. In this study, we investigated the effects of cervical vagotomy and the α7nAChR agonist pnu282987 on CD4(+) T cell differentiation in a murine myocarditis model (BALB/c) infected with coxsackievirus B3 (CVB3). Splenic CD4(+) T cells from CVB3-induced mice obtained and cultured to investigate the potential mechanism of CD4(+) T cell differentiation. Each Th cell subset was analyzed by flow cytometry. Our results showed that right cervical vagotomy increased proportions of Th1 and Th17 cells and decreased proportions of Th2 and Treg cells in the spleen. Vagotomy-induced upregulation of T-bet, Ror-γ, IFN-γ, and IL-17 expression while downregulating the expression of Gata3, Foxp3, and IL-4 in the heart. In addition, we observed upregulated levels of proinflammatory cytokines, aggravated myocardial lesions and cellular infiltration, and worsened cardiac function in VMC mice. Pnu282987 administration reversed these outcomes. Furthermore, vagotomy inhibited JAK2-STAT3 activation and enhanced NF-κB activation in splenic CD4(+) T cells. The CD4(+) T cell differentiation was related to JAK2-STAT3 and NF-κB signal pathways. In conclusion, vagus nerve modulates the inflammatory response by regulating CD4(+) T cell differentiation in response to VMC.
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spelling pubmed-78340892021-02-02 Vagus nerve plays a pivotal role in CD4+ T cell differentiation during CVB3-induced murine acute myocarditis Yue-Chun, Li Gu, Xiao-Hong Li-Sha, Ge Zhou, De-Pu Xing, Chao Guo, Xiao-Ling Pan, Lu-Lu Song, Shi-Yang Yu, Li-Li Chen, Guang-Yi Lin, Jia-Feng Chu, Mao-Ping Virulence Research Paper Abnormalities in CD4(+) T cell (Th cell) differentiation play an important role in the pathogenesis of viral myocarditis (VMC). Our previous studies demonstrated that activation of the cholinergic anti-inflammatory pathway (CAP) alleviated the inflammatory response. In addition, we observed that right cervical vagotomy aggravates VMC by inhibiting CAP. However, the vagus nerve’s effect on differentiation of CD4(+) T cells has not been studied in VMC mice to date. In this study, we investigated the effects of cervical vagotomy and the α7nAChR agonist pnu282987 on CD4(+) T cell differentiation in a murine myocarditis model (BALB/c) infected with coxsackievirus B3 (CVB3). Splenic CD4(+) T cells from CVB3-induced mice obtained and cultured to investigate the potential mechanism of CD4(+) T cell differentiation. Each Th cell subset was analyzed by flow cytometry. Our results showed that right cervical vagotomy increased proportions of Th1 and Th17 cells and decreased proportions of Th2 and Treg cells in the spleen. Vagotomy-induced upregulation of T-bet, Ror-γ, IFN-γ, and IL-17 expression while downregulating the expression of Gata3, Foxp3, and IL-4 in the heart. In addition, we observed upregulated levels of proinflammatory cytokines, aggravated myocardial lesions and cellular infiltration, and worsened cardiac function in VMC mice. Pnu282987 administration reversed these outcomes. Furthermore, vagotomy inhibited JAK2-STAT3 activation and enhanced NF-κB activation in splenic CD4(+) T cells. The CD4(+) T cell differentiation was related to JAK2-STAT3 and NF-κB signal pathways. In conclusion, vagus nerve modulates the inflammatory response by regulating CD4(+) T cell differentiation in response to VMC. Taylor & Francis 2021-01-15 /pmc/articles/PMC7834089/ /pubmed/33380272 http://dx.doi.org/10.1080/21505594.2020.1869384 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Yue-Chun, Li
Gu, Xiao-Hong
Li-Sha, Ge
Zhou, De-Pu
Xing, Chao
Guo, Xiao-Ling
Pan, Lu-Lu
Song, Shi-Yang
Yu, Li-Li
Chen, Guang-Yi
Lin, Jia-Feng
Chu, Mao-Ping
Vagus nerve plays a pivotal role in CD4+ T cell differentiation during CVB3-induced murine acute myocarditis
title Vagus nerve plays a pivotal role in CD4+ T cell differentiation during CVB3-induced murine acute myocarditis
title_full Vagus nerve plays a pivotal role in CD4+ T cell differentiation during CVB3-induced murine acute myocarditis
title_fullStr Vagus nerve plays a pivotal role in CD4+ T cell differentiation during CVB3-induced murine acute myocarditis
title_full_unstemmed Vagus nerve plays a pivotal role in CD4+ T cell differentiation during CVB3-induced murine acute myocarditis
title_short Vagus nerve plays a pivotal role in CD4+ T cell differentiation during CVB3-induced murine acute myocarditis
title_sort vagus nerve plays a pivotal role in cd4+ t cell differentiation during cvb3-induced murine acute myocarditis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834089/
https://www.ncbi.nlm.nih.gov/pubmed/33380272
http://dx.doi.org/10.1080/21505594.2020.1869384
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