Cargando…
Short-range interactions between fibrocytes and CD8(+) T cells in COPD bronchial inflammatory response
Bronchi of chronic obstructive pulmonary disease (COPD) are the site of extensive cell infiltration, allowing persistent contact between resident cells and immune cells. Tissue fibrocytes interaction with CD8(+) T cells and its consequences were investigated using a combination of in situ, in vitro...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371228/ https://www.ncbi.nlm.nih.gov/pubmed/37494277 http://dx.doi.org/10.7554/eLife.85875 |
_version_ | 1785078104349212672 |
---|---|
author | Eyraud, Edmée Maurat, Elise Sac-Epée, Jean-Marc Henrot, Pauline Zysman, Maeva Esteves, Pauline Trian, Thomas Dupuy, Jean-William Leipold, Alexander Saliba, Antoine-Emmanuel Begueret, Hugues Girodet, Pierre-Olivier Thumerel, Matthieu Hustache-Castaing, Romain Marthan, Roger Levet, Florian Vallois, Pierre Contin-Bordes, Cécile Berger, Patrick Dupin, Isabelle |
author_facet | Eyraud, Edmée Maurat, Elise Sac-Epée, Jean-Marc Henrot, Pauline Zysman, Maeva Esteves, Pauline Trian, Thomas Dupuy, Jean-William Leipold, Alexander Saliba, Antoine-Emmanuel Begueret, Hugues Girodet, Pierre-Olivier Thumerel, Matthieu Hustache-Castaing, Romain Marthan, Roger Levet, Florian Vallois, Pierre Contin-Bordes, Cécile Berger, Patrick Dupin, Isabelle |
author_sort | Eyraud, Edmée |
collection | PubMed |
description | Bronchi of chronic obstructive pulmonary disease (COPD) are the site of extensive cell infiltration, allowing persistent contact between resident cells and immune cells. Tissue fibrocytes interaction with CD8(+) T cells and its consequences were investigated using a combination of in situ, in vitro experiments and mathematical modeling. We show that fibrocytes and CD8(+) T cells are found in the vicinity of distal airways and that potential interactions are more frequent in tissues from COPD patients compared to those of control subjects. Increased proximity and clusterization between CD8(+) T cells and fibrocytes are associated with altered lung function. Tissular CD8(+) T cells from COPD patients promote fibrocyte chemotaxis via the CXCL8-CXCR1/2 axis. Live imaging shows that CD8(+) T cells establish short-term interactions with fibrocytes, that trigger CD8(+) T cell proliferation in a CD54- and CD86-dependent manner, pro-inflammatory cytokines production, CD8(+) T cell cytotoxic activity against bronchial epithelial cells and fibrocyte immunomodulatory properties. We defined a computational model describing these intercellular interactions and calibrated the parameters based on our experimental measurements. We show the model’s ability to reproduce histological ex vivo characteristics, and observe an important contribution of fibrocyte-mediated CD8(+) T cell proliferation in COPD development. Using the model to test therapeutic scenarios, we predict a recovery time of several years, and the failure of targeting chemotaxis or interacting processes. Altogether, our study reveals that local interactions between fibrocytes and CD8(+) T cells could jeopardize the balance between protective immunity and chronic inflammation in the bronchi of COPD patients. |
format | Online Article Text |
id | pubmed-10371228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-103712282023-07-27 Short-range interactions between fibrocytes and CD8(+) T cells in COPD bronchial inflammatory response Eyraud, Edmée Maurat, Elise Sac-Epée, Jean-Marc Henrot, Pauline Zysman, Maeva Esteves, Pauline Trian, Thomas Dupuy, Jean-William Leipold, Alexander Saliba, Antoine-Emmanuel Begueret, Hugues Girodet, Pierre-Olivier Thumerel, Matthieu Hustache-Castaing, Romain Marthan, Roger Levet, Florian Vallois, Pierre Contin-Bordes, Cécile Berger, Patrick Dupin, Isabelle eLife Computational and Systems Biology Bronchi of chronic obstructive pulmonary disease (COPD) are the site of extensive cell infiltration, allowing persistent contact between resident cells and immune cells. Tissue fibrocytes interaction with CD8(+) T cells and its consequences were investigated using a combination of in situ, in vitro experiments and mathematical modeling. We show that fibrocytes and CD8(+) T cells are found in the vicinity of distal airways and that potential interactions are more frequent in tissues from COPD patients compared to those of control subjects. Increased proximity and clusterization between CD8(+) T cells and fibrocytes are associated with altered lung function. Tissular CD8(+) T cells from COPD patients promote fibrocyte chemotaxis via the CXCL8-CXCR1/2 axis. Live imaging shows that CD8(+) T cells establish short-term interactions with fibrocytes, that trigger CD8(+) T cell proliferation in a CD54- and CD86-dependent manner, pro-inflammatory cytokines production, CD8(+) T cell cytotoxic activity against bronchial epithelial cells and fibrocyte immunomodulatory properties. We defined a computational model describing these intercellular interactions and calibrated the parameters based on our experimental measurements. We show the model’s ability to reproduce histological ex vivo characteristics, and observe an important contribution of fibrocyte-mediated CD8(+) T cell proliferation in COPD development. Using the model to test therapeutic scenarios, we predict a recovery time of several years, and the failure of targeting chemotaxis or interacting processes. Altogether, our study reveals that local interactions between fibrocytes and CD8(+) T cells could jeopardize the balance between protective immunity and chronic inflammation in the bronchi of COPD patients. eLife Sciences Publications, Ltd 2023-07-26 /pmc/articles/PMC10371228/ /pubmed/37494277 http://dx.doi.org/10.7554/eLife.85875 Text en © 2023, Eyraud et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Computational and Systems Biology Eyraud, Edmée Maurat, Elise Sac-Epée, Jean-Marc Henrot, Pauline Zysman, Maeva Esteves, Pauline Trian, Thomas Dupuy, Jean-William Leipold, Alexander Saliba, Antoine-Emmanuel Begueret, Hugues Girodet, Pierre-Olivier Thumerel, Matthieu Hustache-Castaing, Romain Marthan, Roger Levet, Florian Vallois, Pierre Contin-Bordes, Cécile Berger, Patrick Dupin, Isabelle Short-range interactions between fibrocytes and CD8(+) T cells in COPD bronchial inflammatory response |
title | Short-range interactions between fibrocytes and CD8(+) T cells in COPD bronchial inflammatory response |
title_full | Short-range interactions between fibrocytes and CD8(+) T cells in COPD bronchial inflammatory response |
title_fullStr | Short-range interactions between fibrocytes and CD8(+) T cells in COPD bronchial inflammatory response |
title_full_unstemmed | Short-range interactions between fibrocytes and CD8(+) T cells in COPD bronchial inflammatory response |
title_short | Short-range interactions between fibrocytes and CD8(+) T cells in COPD bronchial inflammatory response |
title_sort | short-range interactions between fibrocytes and cd8(+) t cells in copd bronchial inflammatory response |
topic | Computational and Systems Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371228/ https://www.ncbi.nlm.nih.gov/pubmed/37494277 http://dx.doi.org/10.7554/eLife.85875 |
work_keys_str_mv | AT eyraudedmee shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT mauratelise shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT sacepeejeanmarc shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT henrotpauline shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT zysmanmaeva shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT estevespauline shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT trianthomas shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT dupuyjeanwilliam shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT leipoldalexander shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT salibaantoineemmanuel shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT beguerethugues shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT girodetpierreolivier shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT thumerelmatthieu shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT hustachecastaingromain shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT marthanroger shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT levetflorian shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT valloispierre shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT continbordescecile shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT bergerpatrick shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse AT dupinisabelle shortrangeinteractionsbetweenfibrocytesandcd8tcellsincopdbronchialinflammatoryresponse |