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Immunostimulatory Endogenous Nucleic Acids Perpetuate Interface Dermatitis—Translation of Pathogenic Fundamentals Into an In Vitro Model

Interface dermatitis is a histopathological pattern mirroring a distinct cytotoxic immune response shared by a number of clinically diverse inflammatory skin diseases amongst which lichen planus and cutaneous lupus erythematosus are considered prototypic. Interface dermatitis is characterized by pro...

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Autores principales: Braegelmann, Christine, Fetter, Tanja, Niebel, Dennis, Dietz, Lara, Bieber, Thomas, Wenzel, Joerg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831152/
https://www.ncbi.nlm.nih.gov/pubmed/33505404
http://dx.doi.org/10.3389/fimmu.2020.622511
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author Braegelmann, Christine
Fetter, Tanja
Niebel, Dennis
Dietz, Lara
Bieber, Thomas
Wenzel, Joerg
author_facet Braegelmann, Christine
Fetter, Tanja
Niebel, Dennis
Dietz, Lara
Bieber, Thomas
Wenzel, Joerg
author_sort Braegelmann, Christine
collection PubMed
description Interface dermatitis is a histopathological pattern mirroring a distinct cytotoxic immune response shared by a number of clinically diverse inflammatory skin diseases amongst which lichen planus and cutaneous lupus erythematosus are considered prototypic. Interface dermatitis is characterized by pronounced cytotoxic immune cell infiltration and necroptotic keratinocytes at the dermoepidermal junction. The initial inflammatory reaction is established by cytotoxic immune cells that express CXC chemokine receptor 3 and lesional keratinocytes that produce corresponding ligands, CXC motif ligands 9/10/11, recruiting the effector cells to the site of inflammation. During the resulting anti-epithelial attack, endogenous immune complexes and nucleic acids are released from perishing keratinocytes, which are then perceived by the innate immune system as danger signals. Keratinocytes express a distinct signature of pattern recognition receptors and binding of endogenous nucleic acid motifs to these receptors results in interferon-mediated immune responses and further enhancement of CXC chemokine receptor 3 ligand production. In this perspective article, we will discuss the role of innate nucleic acid sensing as a common mechanism in the perpetuation of clinically heterogeneous diseases featuring interface dermatitis based on own data and a review of the literature. Furthermore, we will introduce a keratinocyte-specific in vitro model of interface dermatitis as follows: Stimulation of human keratinocytes with endogenous nucleic acids alone and in combination with interferon gamma leads to pronounced production of distinct cytokines, which are essential in the pathogenesis of interface dermatitis. This experimental approach bears the capability to investigate potential therapeutics in this group of diseases with unmet medical need.
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spelling pubmed-78311522021-01-26 Immunostimulatory Endogenous Nucleic Acids Perpetuate Interface Dermatitis—Translation of Pathogenic Fundamentals Into an In Vitro Model Braegelmann, Christine Fetter, Tanja Niebel, Dennis Dietz, Lara Bieber, Thomas Wenzel, Joerg Front Immunol Immunology Interface dermatitis is a histopathological pattern mirroring a distinct cytotoxic immune response shared by a number of clinically diverse inflammatory skin diseases amongst which lichen planus and cutaneous lupus erythematosus are considered prototypic. Interface dermatitis is characterized by pronounced cytotoxic immune cell infiltration and necroptotic keratinocytes at the dermoepidermal junction. The initial inflammatory reaction is established by cytotoxic immune cells that express CXC chemokine receptor 3 and lesional keratinocytes that produce corresponding ligands, CXC motif ligands 9/10/11, recruiting the effector cells to the site of inflammation. During the resulting anti-epithelial attack, endogenous immune complexes and nucleic acids are released from perishing keratinocytes, which are then perceived by the innate immune system as danger signals. Keratinocytes express a distinct signature of pattern recognition receptors and binding of endogenous nucleic acid motifs to these receptors results in interferon-mediated immune responses and further enhancement of CXC chemokine receptor 3 ligand production. In this perspective article, we will discuss the role of innate nucleic acid sensing as a common mechanism in the perpetuation of clinically heterogeneous diseases featuring interface dermatitis based on own data and a review of the literature. Furthermore, we will introduce a keratinocyte-specific in vitro model of interface dermatitis as follows: Stimulation of human keratinocytes with endogenous nucleic acids alone and in combination with interferon gamma leads to pronounced production of distinct cytokines, which are essential in the pathogenesis of interface dermatitis. This experimental approach bears the capability to investigate potential therapeutics in this group of diseases with unmet medical need. Frontiers Media S.A. 2021-01-11 /pmc/articles/PMC7831152/ /pubmed/33505404 http://dx.doi.org/10.3389/fimmu.2020.622511 Text en Copyright © 2021 Braegelmann, Fetter, Niebel, Dietz, Bieber and Wenzel http://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
Braegelmann, Christine
Fetter, Tanja
Niebel, Dennis
Dietz, Lara
Bieber, Thomas
Wenzel, Joerg
Immunostimulatory Endogenous Nucleic Acids Perpetuate Interface Dermatitis—Translation of Pathogenic Fundamentals Into an In Vitro Model
title Immunostimulatory Endogenous Nucleic Acids Perpetuate Interface Dermatitis—Translation of Pathogenic Fundamentals Into an In Vitro Model
title_full Immunostimulatory Endogenous Nucleic Acids Perpetuate Interface Dermatitis—Translation of Pathogenic Fundamentals Into an In Vitro Model
title_fullStr Immunostimulatory Endogenous Nucleic Acids Perpetuate Interface Dermatitis—Translation of Pathogenic Fundamentals Into an In Vitro Model
title_full_unstemmed Immunostimulatory Endogenous Nucleic Acids Perpetuate Interface Dermatitis—Translation of Pathogenic Fundamentals Into an In Vitro Model
title_short Immunostimulatory Endogenous Nucleic Acids Perpetuate Interface Dermatitis—Translation of Pathogenic Fundamentals Into an In Vitro Model
title_sort immunostimulatory endogenous nucleic acids perpetuate interface dermatitis—translation of pathogenic fundamentals into an in vitro model
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831152/
https://www.ncbi.nlm.nih.gov/pubmed/33505404
http://dx.doi.org/10.3389/fimmu.2020.622511
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