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Lung Epithelial CYP1 Activity Regulates Aryl Hydrocarbon Receptor Dependent Allergic Airway Inflammation

The lung epithelial barrier serves as a guardian towards environmental insults and responds to allergen encounter with a cascade of immune reactions that can possibly lead to inflammation. Whether the environmental sensor aryl hydrocarbon receptor (AhR) together with its downstream targets cytochrom...

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Autores principales: Alessandrini, Francesca, de Jong, Renske, Wimmer, Maria, Maier, Ann-Marie, Fernandez, Isis, Hils, Miriam, Buters, Jeroen T., Biedermann, Tilo, Zissler, Ulrich M., Hoffmann, Christian, Esser-von-Bieren, Julia, Schmidt-Weber, Carsten B., Ohnmacht, Caspar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207268/
https://www.ncbi.nlm.nih.gov/pubmed/35734174
http://dx.doi.org/10.3389/fimmu.2022.901194
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author Alessandrini, Francesca
de Jong, Renske
Wimmer, Maria
Maier, Ann-Marie
Fernandez, Isis
Hils, Miriam
Buters, Jeroen T.
Biedermann, Tilo
Zissler, Ulrich M.
Hoffmann, Christian
Esser-von-Bieren, Julia
Schmidt-Weber, Carsten B.
Ohnmacht, Caspar
author_facet Alessandrini, Francesca
de Jong, Renske
Wimmer, Maria
Maier, Ann-Marie
Fernandez, Isis
Hils, Miriam
Buters, Jeroen T.
Biedermann, Tilo
Zissler, Ulrich M.
Hoffmann, Christian
Esser-von-Bieren, Julia
Schmidt-Weber, Carsten B.
Ohnmacht, Caspar
author_sort Alessandrini, Francesca
collection PubMed
description The lung epithelial barrier serves as a guardian towards environmental insults and responds to allergen encounter with a cascade of immune reactions that can possibly lead to inflammation. Whether the environmental sensor aryl hydrocarbon receptor (AhR) together with its downstream targets cytochrome P450 (CYP1) family members contribute to the regulation of allergic airway inflammation remains unexplored. By employing knockout mice for AhR and for single CYP1 family members, we found that AhR(-/-) and CYP1B1(-/-) but not CYP1A1(-/-) or CYP1A2(-/-) animals display enhanced allergic airway inflammation compared to WT. Expression analysis, immunofluorescence staining of murine and human lung sections and bone marrow chimeras suggest an important role of CYP1B1 in non-hematopoietic lung epithelial cells to prevent exacerbation of allergic airway inflammation. Transcriptional analysis of murine and human lung epithelial cells indicates a functional link of AhR to barrier protection/inflammatory mediator signaling upon allergen challenge. In contrast, CYP1B1 deficiency leads to enhanced expression and activity of CYP1A1 in lung epithelial cells and to an increased availability of the AhR ligand kynurenic acid following allergen challenge. Thus, differential CYP1 family member expression and signaling via the AhR in epithelial cells represents an immunoregulatory layer protecting the lung from exacerbation of allergic airway inflammation.
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spelling pubmed-92072682022-06-21 Lung Epithelial CYP1 Activity Regulates Aryl Hydrocarbon Receptor Dependent Allergic Airway Inflammation Alessandrini, Francesca de Jong, Renske Wimmer, Maria Maier, Ann-Marie Fernandez, Isis Hils, Miriam Buters, Jeroen T. Biedermann, Tilo Zissler, Ulrich M. Hoffmann, Christian Esser-von-Bieren, Julia Schmidt-Weber, Carsten B. Ohnmacht, Caspar Front Immunol Immunology The lung epithelial barrier serves as a guardian towards environmental insults and responds to allergen encounter with a cascade of immune reactions that can possibly lead to inflammation. Whether the environmental sensor aryl hydrocarbon receptor (AhR) together with its downstream targets cytochrome P450 (CYP1) family members contribute to the regulation of allergic airway inflammation remains unexplored. By employing knockout mice for AhR and for single CYP1 family members, we found that AhR(-/-) and CYP1B1(-/-) but not CYP1A1(-/-) or CYP1A2(-/-) animals display enhanced allergic airway inflammation compared to WT. Expression analysis, immunofluorescence staining of murine and human lung sections and bone marrow chimeras suggest an important role of CYP1B1 in non-hematopoietic lung epithelial cells to prevent exacerbation of allergic airway inflammation. Transcriptional analysis of murine and human lung epithelial cells indicates a functional link of AhR to barrier protection/inflammatory mediator signaling upon allergen challenge. In contrast, CYP1B1 deficiency leads to enhanced expression and activity of CYP1A1 in lung epithelial cells and to an increased availability of the AhR ligand kynurenic acid following allergen challenge. Thus, differential CYP1 family member expression and signaling via the AhR in epithelial cells represents an immunoregulatory layer protecting the lung from exacerbation of allergic airway inflammation. Frontiers Media S.A. 2022-06-06 /pmc/articles/PMC9207268/ /pubmed/35734174 http://dx.doi.org/10.3389/fimmu.2022.901194 Text en Copyright © 2022 Alessandrini, de Jong, Wimmer, Maier, Fernandez, Hils, Buters, Biedermann, Zissler, Hoffmann, Esser-von-Bieren, Schmidt-Weber and Ohnmacht 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
Alessandrini, Francesca
de Jong, Renske
Wimmer, Maria
Maier, Ann-Marie
Fernandez, Isis
Hils, Miriam
Buters, Jeroen T.
Biedermann, Tilo
Zissler, Ulrich M.
Hoffmann, Christian
Esser-von-Bieren, Julia
Schmidt-Weber, Carsten B.
Ohnmacht, Caspar
Lung Epithelial CYP1 Activity Regulates Aryl Hydrocarbon Receptor Dependent Allergic Airway Inflammation
title Lung Epithelial CYP1 Activity Regulates Aryl Hydrocarbon Receptor Dependent Allergic Airway Inflammation
title_full Lung Epithelial CYP1 Activity Regulates Aryl Hydrocarbon Receptor Dependent Allergic Airway Inflammation
title_fullStr Lung Epithelial CYP1 Activity Regulates Aryl Hydrocarbon Receptor Dependent Allergic Airway Inflammation
title_full_unstemmed Lung Epithelial CYP1 Activity Regulates Aryl Hydrocarbon Receptor Dependent Allergic Airway Inflammation
title_short Lung Epithelial CYP1 Activity Regulates Aryl Hydrocarbon Receptor Dependent Allergic Airway Inflammation
title_sort lung epithelial cyp1 activity regulates aryl hydrocarbon receptor dependent allergic airway inflammation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207268/
https://www.ncbi.nlm.nih.gov/pubmed/35734174
http://dx.doi.org/10.3389/fimmu.2022.901194
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