Influence of FLG loss-of-function mutations in host-microbe interactions during atopic skin inflammation.

Dermatitis, Atopic / metabolism Filaggrin Proteins / metabolism Host Microbial Interactions / genetics Humans Inflammation / genetics Intermediate Filament Proteins / genetics Mutation Skin / metabolism Staphylococcus aureus
Atopic dermatitis Barrier function Filaggrin Microbiome Multi-omics Transcriptome

Journal

Journal of dermatological science
ISSN: 1873-569X
Titre abrégé: J Dermatol Sci
Pays: Netherlands
ID NLM: 9011485

Informations de publication

Date de publication:
Jun 2022
Historique:
received: 06 12 2021
revised: 22 03 2022
accepted: 08 04 2022
pubmed: 11 5 2022
medline: 22 6 2022
entrez: 10 5 2022
Statut: ppublish

Résumé

Loss-of-function mutations in the filaggrin (FLG) gene directly alter skin barrier function and critically influence atopic inflammation. While skin barrier dysfunction, Th2-associated inflammation and bacterial dysbiosis are well-known characteristics of atopic dermatitis (AD), the mechanisms interconnecting genotype, transcriptome and microbiome remain largely elusive. In-depth analysis of FLG genotype-associated skin gene expression alterations and host-microbe interactions in AD. Multi-omics characterization of a cohort of AD patients carrying heterozygous loss-of-function mutations in the FLG gene (AD In the context of filaggrin dysfunction, the transcriptome was characterized by dysregulation of barrier function and water homeostasis, while the lesional skin of AD Our integrative approach provides molecular insights for the concept that FLG loss-of-function mutations are a genetic shortcut to atopic inflammation and unravels the complex interplay between genotype, transcriptome and microbiome in the human holobiont.

Sections du résumé

BACKGROUND BACKGROUND
Loss-of-function mutations in the filaggrin (FLG) gene directly alter skin barrier function and critically influence atopic inflammation. While skin barrier dysfunction, Th2-associated inflammation and bacterial dysbiosis are well-known characteristics of atopic dermatitis (AD), the mechanisms interconnecting genotype, transcriptome and microbiome remain largely elusive.
OBJECTIVE OBJECTIVE
In-depth analysis of FLG genotype-associated skin gene expression alterations and host-microbe interactions in AD.
METHODS METHODS
Multi-omics characterization of a cohort of AD patients carrying heterozygous loss-of-function mutations in the FLG gene (AD
RESULTS RESULTS
In the context of filaggrin dysfunction, the transcriptome was characterized by dysregulation of barrier function and water homeostasis, while the lesional skin of AD
CONCLUSIONS CONCLUSIONS
Our integrative approach provides molecular insights for the concept that FLG loss-of-function mutations are a genetic shortcut to atopic inflammation and unravels the complex interplay between genotype, transcriptome and microbiome in the human holobiont.

Identifiants

DOI: 10.1016/j.jdermsci.2022.04.007 PMID: 35537882
pubmed: 35537882
pii: S0923-1811(22)00097-4
doi: 10.1016/j.jdermsci.2022.04.007
pii:
doi:

Substances chimiques

FLG protein, human 0
Filaggrin Proteins 0
Intermediate Filament Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

132-140

Informations de copyright

Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.

Auteurs

Peter Oláh (P)

Department of Dermatology, University Hospital Duesseldorf, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany; Department of Dermatology, Venereology and Oncodermatology, Medical Faculty, University of Pécs, Hungary.

Eszter Szlávicz (E)

Department of Dermatology, Venereology and Oncodermatology, Medical Faculty, University of Pécs, Hungary.

Marcus Kuchner (M)

Department of Dermatology, University Hospital Duesseldorf, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.

Jana Nemmer (J)

Department of Dermatology, University Hospital Duesseldorf, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.

Patrick Zeeuwen (P)

Department of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.

Alain Lefèvre-Utile (A)

Université de Paris, Inserm, U976 HIPI Unit, Institut de Recherche Saint-Louis, Paris, France; Assistance Publique-Hôpitaux de Paris (APHP), General Pediatric and Pediatric Emergency Department, Jean Verdier Hospital, Bondy, France.

Nanna Fyhrquist (N)

Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Stefanie Prast-Nielsen (S)

Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Tiina Skoog (T)

Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.

Angela Serra (A)

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Institute of Biosciences and Medical Technologies (BioMediTech), Tampere, University, Finland.

Elke Rodríguez (E)

Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.

Ulrike Raap (U)

Department of Dermatology, University Hospital Oldenburg, Germany.

Stephan Meller (S)

Department of Dermatology, University Hospital Duesseldorf, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.

Rolland Gyulai (R)

Department of Dermatology, Venereology and Oncodermatology, Medical Faculty, University of Pécs, Hungary.

Philippe Hupé (P)

INSERM U900, CNRS UMR144, Institut Curie, Mine Paris Tech, Paris, France.

Juha Kere (J)

Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden; Stem Cells and Metabolism Research Program, Folkhälsan Research Institute, University of Helsinki, Helsinki, Finland.

Francesca Levi-Schaffer (F)

Pharmacology and Experimental Therapeutics Unit, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.

Sophia Tsoka (S)

Department of Informatics, Faculty of Natural and Mathematical Sciences, Kings College London, London, United Kingdom.

Helen Alexander (H)

St John's Institute of Dermatology, Faculty of Medicine and Life Sciences, Kings College London, London, United Kingdom.

Frank O Nestle (FO)

St John's Institute of Dermatology, Faculty of Medicine and Life Sciences, Kings College London, London, United Kingdom.

Jens M Schröder (JM)

Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.

Stephan Weidinger (S)

Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.

Ellen van den Bogaard (E)

Department of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.

Vassili Soumelis (V)

Université de Paris, Inserm, U976 HIPI Unit, Institut de Recherche Saint-Louis, Paris, France; Laboratoire d'Immunologie et Histocompatibilité, AP-HP, Hôpital St Louis, Paris, France.

Dario Greco (D)

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Institute of Biosciences and Medical Technologies (BioMediTech), Tampere, University, Finland; Institute of Biotechnology, University of Helsinki, Helsinki, Finland.

Jonathan Barker (J)

St John's Institute of Dermatology, Faculty of Medicine and Life Sciences, Kings College London, London, United Kingdom.

Antti Lauerma (A)

Department of Dermatology, Allergology and Venereology, Inflammation Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Annamari Ranki (A)

Department of Dermatology, Allergology and Venereology, Inflammation Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Björn Andersson (B)

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Harri Alenius (H)

Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Bernhard Homey (B)

Department of Dermatology, University Hospital Duesseldorf, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany. Electronic address: bernhard.homey@med.uni-duesseldorf.d.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité immédiate › Eczéma atopique › Influence of FLG loss-of-function mutations in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines S100 › Protéines filaggrine › Influence of FLG loss-of-function mutations in...
questionsmedicales.fr › Phénomènes biologiques › Interactions hôte-microbes › Influence of FLG loss-of-function mutations in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Influence of FLG loss-of-function mutations in...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Influence of FLG loss-of-function mutations in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines de filaments intermédiaires › Influence of FLG loss-of-function mutations in...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Influence of FLG loss-of-function mutations in...
questionsmedicales.fr › Système tégumentaire › Peau › Influence of FLG loss-of-function mutations in...
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Cocci à Gram positif › Staphylococcaceae › Staphylococcus › Staphylococcus aureus › Influence of FLG loss-of-function mutations in...