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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-7831152 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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