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“Outside-to-inside,” “inside-to-outside,” and “intrinsic” endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations

Permeability barrier disruption has been shown to induce immunological alterations (i.e., an “outside-to-inside” pathogenic mechanism). Conversely, several inflammatory and immunological mechanisms reportedly interrupt permeability barrier homeostasis (i.e., an “inside-to-outside” pathogenic mechani...

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Autores principales: Hatano, Yutaka, Elias, Peter M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10451066/
https://www.ncbi.nlm.nih.gov/pubmed/37638035
http://dx.doi.org/10.3389/fimmu.2023.1239251
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author Hatano, Yutaka
Elias, Peter M.
author_facet Hatano, Yutaka
Elias, Peter M.
author_sort Hatano, Yutaka
collection PubMed
description Permeability barrier disruption has been shown to induce immunological alterations (i.e., an “outside-to-inside” pathogenic mechanism). Conversely, several inflammatory and immunological mechanisms reportedly interrupt permeability barrier homeostasis (i.e., an “inside-to-outside” pathogenic mechanism). It is now widely recognized that alterations of even a single molecule in keratinocytes can lead to not only permeability barrier dysfunction but also to immunological alterations. Such a simultaneous, bidirectional functional change by keratinocytes is herein named an “intrinsic” pathogenic mechanism. Molecules and/or pathways involved in this mechanism could be important not only as factors in disease pathogenesis but also as potential therapeutic targets for inflammatory cutaneous diseases, such as atopic dermatitis, psoriasis, and prurigo nodularis. Elevation of skin surface pH following permeability barrier abrogation comprises one of the key pathogenic phenomena of the “outside-to-inside” mechanism. Not only type 2 cytokines (e.g., IL-4, IL-13, IL-31) but also type 1 (e.g. IFN-γ), and type 3 (e.g., IL-17, IL-22) as well as several other inflammatory factors (e.g. histamine) can disrupt permeability barrier homeostasis and are all considered part of the “inside-to-outside” mechanism. Finally, examples of molecules relevant to the “intrinsic” pathogenic mechanism include keratin 1, filaggrin, and peroxisome proliferator-activated receptor-α (PPARα).
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spelling pubmed-104510662023-08-26 “Outside-to-inside,” “inside-to-outside,” and “intrinsic” endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations Hatano, Yutaka Elias, Peter M. Front Immunol Immunology Permeability barrier disruption has been shown to induce immunological alterations (i.e., an “outside-to-inside” pathogenic mechanism). Conversely, several inflammatory and immunological mechanisms reportedly interrupt permeability barrier homeostasis (i.e., an “inside-to-outside” pathogenic mechanism). It is now widely recognized that alterations of even a single molecule in keratinocytes can lead to not only permeability barrier dysfunction but also to immunological alterations. Such a simultaneous, bidirectional functional change by keratinocytes is herein named an “intrinsic” pathogenic mechanism. Molecules and/or pathways involved in this mechanism could be important not only as factors in disease pathogenesis but also as potential therapeutic targets for inflammatory cutaneous diseases, such as atopic dermatitis, psoriasis, and prurigo nodularis. Elevation of skin surface pH following permeability barrier abrogation comprises one of the key pathogenic phenomena of the “outside-to-inside” mechanism. Not only type 2 cytokines (e.g., IL-4, IL-13, IL-31) but also type 1 (e.g. IFN-γ), and type 3 (e.g., IL-17, IL-22) as well as several other inflammatory factors (e.g. histamine) can disrupt permeability barrier homeostasis and are all considered part of the “inside-to-outside” mechanism. Finally, examples of molecules relevant to the “intrinsic” pathogenic mechanism include keratin 1, filaggrin, and peroxisome proliferator-activated receptor-α (PPARα). Frontiers Media S.A. 2023-08-11 /pmc/articles/PMC10451066/ /pubmed/37638035 http://dx.doi.org/10.3389/fimmu.2023.1239251 Text en Copyright © 2023 Hatano and Elias 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
Hatano, Yutaka
Elias, Peter M.
“Outside-to-inside,” “inside-to-outside,” and “intrinsic” endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations
title “Outside-to-inside,” “inside-to-outside,” and “intrinsic” endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations
title_full “Outside-to-inside,” “inside-to-outside,” and “intrinsic” endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations
title_fullStr “Outside-to-inside,” “inside-to-outside,” and “intrinsic” endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations
title_full_unstemmed “Outside-to-inside,” “inside-to-outside,” and “intrinsic” endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations
title_short “Outside-to-inside,” “inside-to-outside,” and “intrinsic” endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations
title_sort “outside-to-inside,” “inside-to-outside,” and “intrinsic” endogenous pathogenic mechanisms in atopic dermatitis: keratinocytes as the key functional cells involved in both permeability barrier dysfunction and immunological alterations
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10451066/
https://www.ncbi.nlm.nih.gov/pubmed/37638035
http://dx.doi.org/10.3389/fimmu.2023.1239251
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