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Dermal fibroblasts are the key sensors of aseptic skin inflammation through interleukin 1 release by lesioned keratinocytes

IL-1 plays a crucial role in triggering sterile inflammation following tissue injury. Although most studies associate IL-1 release by injured cells to the recruitment of neutrophils for tissue repair, the inflammatory cascade involves several molecular and cellular actors whose role remains to be sp...

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Autores principales: Cordier-Dirikoc, Sevda, Pedretti, Nathalie, Garnier, Julien, Clarhaut-Charreau, Sandrine, Ryffel, Bernhard, Morel, Franck, Bernard, François-Xavier, Hamon de Almeida, Valérie, Lecron, Jean-Claude, Jégou, Jean-François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576869/
https://www.ncbi.nlm.nih.gov/pubmed/36268013
http://dx.doi.org/10.3389/fimmu.2022.984045
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author Cordier-Dirikoc, Sevda
Pedretti, Nathalie
Garnier, Julien
Clarhaut-Charreau, Sandrine
Ryffel, Bernhard
Morel, Franck
Bernard, François-Xavier
Hamon de Almeida, Valérie
Lecron, Jean-Claude
Jégou, Jean-François
author_facet Cordier-Dirikoc, Sevda
Pedretti, Nathalie
Garnier, Julien
Clarhaut-Charreau, Sandrine
Ryffel, Bernhard
Morel, Franck
Bernard, François-Xavier
Hamon de Almeida, Valérie
Lecron, Jean-Claude
Jégou, Jean-François
author_sort Cordier-Dirikoc, Sevda
collection PubMed
description IL-1 plays a crucial role in triggering sterile inflammation following tissue injury. Although most studies associate IL-1 release by injured cells to the recruitment of neutrophils for tissue repair, the inflammatory cascade involves several molecular and cellular actors whose role remains to be specified. In the present study, we identified dermal fibroblasts among the IL-1R1-expressing skin cells as key sensors of IL-1 released by injured keratinocytes. After in vitro stimulation by recombinant cytokines or protein extracts of lysed keratinocytes containing high concentrations of IL-1, we show that dermal fibroblasts are by far the most IL-1-responsive cells compared to keratinocytes, melanocytes and endothelial cells. Fibroblasts have the property to respond to very low concentrations of IL-1 (from 10 fg/ml), even in the presence of 100-fold higher concentrations of IL-1RA, by increasing their expression of chemokines such as IL-8 for neutrophil recruitment. The capacity of IL-1-stimulated fibroblasts to attract neutrophils has been demonstrated both in vitro using cell migration assay and in vivo using a model of superficial epidermal lesion in IL-1R1-deficient mice which harbored reduced expression of inflammatory mediators and neutrophil skin infiltration. Together, our results shed a light on dermal fibroblasts as key relay cells in the chain of sterile inflammation induced after epidermal lesion.
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spelling pubmed-95768692022-10-19 Dermal fibroblasts are the key sensors of aseptic skin inflammation through interleukin 1 release by lesioned keratinocytes Cordier-Dirikoc, Sevda Pedretti, Nathalie Garnier, Julien Clarhaut-Charreau, Sandrine Ryffel, Bernhard Morel, Franck Bernard, François-Xavier Hamon de Almeida, Valérie Lecron, Jean-Claude Jégou, Jean-François Front Immunol Immunology IL-1 plays a crucial role in triggering sterile inflammation following tissue injury. Although most studies associate IL-1 release by injured cells to the recruitment of neutrophils for tissue repair, the inflammatory cascade involves several molecular and cellular actors whose role remains to be specified. In the present study, we identified dermal fibroblasts among the IL-1R1-expressing skin cells as key sensors of IL-1 released by injured keratinocytes. After in vitro stimulation by recombinant cytokines or protein extracts of lysed keratinocytes containing high concentrations of IL-1, we show that dermal fibroblasts are by far the most IL-1-responsive cells compared to keratinocytes, melanocytes and endothelial cells. Fibroblasts have the property to respond to very low concentrations of IL-1 (from 10 fg/ml), even in the presence of 100-fold higher concentrations of IL-1RA, by increasing their expression of chemokines such as IL-8 for neutrophil recruitment. The capacity of IL-1-stimulated fibroblasts to attract neutrophils has been demonstrated both in vitro using cell migration assay and in vivo using a model of superficial epidermal lesion in IL-1R1-deficient mice which harbored reduced expression of inflammatory mediators and neutrophil skin infiltration. Together, our results shed a light on dermal fibroblasts as key relay cells in the chain of sterile inflammation induced after epidermal lesion. Frontiers Media S.A. 2022-10-03 /pmc/articles/PMC9576869/ /pubmed/36268013 http://dx.doi.org/10.3389/fimmu.2022.984045 Text en Copyright © 2022 Cordier-Dirikoc, Pedretti, Garnier, Clarhaut-Charreau, Ryffel, Morel, Bernard, Hamon de Almeida, Lecron and Jégou https://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
Cordier-Dirikoc, Sevda
Pedretti, Nathalie
Garnier, Julien
Clarhaut-Charreau, Sandrine
Ryffel, Bernhard
Morel, Franck
Bernard, François-Xavier
Hamon de Almeida, Valérie
Lecron, Jean-Claude
Jégou, Jean-François
Dermal fibroblasts are the key sensors of aseptic skin inflammation through interleukin 1 release by lesioned keratinocytes
title Dermal fibroblasts are the key sensors of aseptic skin inflammation through interleukin 1 release by lesioned keratinocytes
title_full Dermal fibroblasts are the key sensors of aseptic skin inflammation through interleukin 1 release by lesioned keratinocytes
title_fullStr Dermal fibroblasts are the key sensors of aseptic skin inflammation through interleukin 1 release by lesioned keratinocytes
title_full_unstemmed Dermal fibroblasts are the key sensors of aseptic skin inflammation through interleukin 1 release by lesioned keratinocytes
title_short Dermal fibroblasts are the key sensors of aseptic skin inflammation through interleukin 1 release by lesioned keratinocytes
title_sort dermal fibroblasts are the key sensors of aseptic skin inflammation through interleukin 1 release by lesioned keratinocytes
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576869/
https://www.ncbi.nlm.nih.gov/pubmed/36268013
http://dx.doi.org/10.3389/fimmu.2022.984045
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