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Physiological strength electric fields modulate human T cell activation and polarisation
The factors and signals driving T cell activation and polarisation during immune responses have been studied mainly at the level of cells and chemical mediators. Here we describe a physical driver of these processes in the form of physiological-strength electric fields (EFs). EFs are generated at si...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879562/ https://www.ncbi.nlm.nih.gov/pubmed/31772211 http://dx.doi.org/10.1038/s41598-019-53898-5 |
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author | Arnold, Christina E. Rajnicek, Ann M. Hoare, Joseph I. Pokharel, Swechha Mainali Mccaig, Colin D. Barker, Robert N. Wilson, Heather M. |
author_facet | Arnold, Christina E. Rajnicek, Ann M. Hoare, Joseph I. Pokharel, Swechha Mainali Mccaig, Colin D. Barker, Robert N. Wilson, Heather M. |
author_sort | Arnold, Christina E. |
collection | PubMed |
description | The factors and signals driving T cell activation and polarisation during immune responses have been studied mainly at the level of cells and chemical mediators. Here we describe a physical driver of these processes in the form of physiological-strength electric fields (EFs). EFs are generated at sites where epithelium is disrupted (e.g. wounded skin/bronchial epithelia) and where T cells frequently are present. Using live-cell imaging, we show human primary T cells migrate directionally to the cathode in low strength (50/150 mV/mm) EFs. Strikingly, we show for the first time that EFs significantly downregulate T cell activation following stimulation with antigen-activated APCs or anti-CD3/CD28 antibodies, as demonstrated by decreased IL-2 secretion and proliferation. These EF-induced functional changes were accompanied by a significant dampening of CD4(+) T cell polarisation. Expression of critical markers of the Th17 lineage, RORγt and IL-17, and the Th17 polarisation mediator phospho-STAT3 were reduced significantly, while STAT1, ERK and c-Jun phosphorylation were comparatively unaffected suggesting STAT3 modulation by EFs as one mechanism driving effects. Overall, we identify electrical signals as important contributors to the co-ordination and regulation of human T cell functions, paving the way for a new research area into effects of naturally occurring and clinically-applied EFs in conditions where control of T cell activity is paramount. |
format | Online Article Text |
id | pubmed-6879562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68795622019-12-05 Physiological strength electric fields modulate human T cell activation and polarisation Arnold, Christina E. Rajnicek, Ann M. Hoare, Joseph I. Pokharel, Swechha Mainali Mccaig, Colin D. Barker, Robert N. Wilson, Heather M. Sci Rep Article The factors and signals driving T cell activation and polarisation during immune responses have been studied mainly at the level of cells and chemical mediators. Here we describe a physical driver of these processes in the form of physiological-strength electric fields (EFs). EFs are generated at sites where epithelium is disrupted (e.g. wounded skin/bronchial epithelia) and where T cells frequently are present. Using live-cell imaging, we show human primary T cells migrate directionally to the cathode in low strength (50/150 mV/mm) EFs. Strikingly, we show for the first time that EFs significantly downregulate T cell activation following stimulation with antigen-activated APCs or anti-CD3/CD28 antibodies, as demonstrated by decreased IL-2 secretion and proliferation. These EF-induced functional changes were accompanied by a significant dampening of CD4(+) T cell polarisation. Expression of critical markers of the Th17 lineage, RORγt and IL-17, and the Th17 polarisation mediator phospho-STAT3 were reduced significantly, while STAT1, ERK and c-Jun phosphorylation were comparatively unaffected suggesting STAT3 modulation by EFs as one mechanism driving effects. Overall, we identify electrical signals as important contributors to the co-ordination and regulation of human T cell functions, paving the way for a new research area into effects of naturally occurring and clinically-applied EFs in conditions where control of T cell activity is paramount. Nature Publishing Group UK 2019-11-26 /pmc/articles/PMC6879562/ /pubmed/31772211 http://dx.doi.org/10.1038/s41598-019-53898-5 Text en © The Author(s) 2019 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/. |
spellingShingle | Article Arnold, Christina E. Rajnicek, Ann M. Hoare, Joseph I. Pokharel, Swechha Mainali Mccaig, Colin D. Barker, Robert N. Wilson, Heather M. Physiological strength electric fields modulate human T cell activation and polarisation |
title | Physiological strength electric fields modulate human T cell activation and polarisation |
title_full | Physiological strength electric fields modulate human T cell activation and polarisation |
title_fullStr | Physiological strength electric fields modulate human T cell activation and polarisation |
title_full_unstemmed | Physiological strength electric fields modulate human T cell activation and polarisation |
title_short | Physiological strength electric fields modulate human T cell activation and polarisation |
title_sort | physiological strength electric fields modulate human t cell activation and polarisation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879562/ https://www.ncbi.nlm.nih.gov/pubmed/31772211 http://dx.doi.org/10.1038/s41598-019-53898-5 |
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