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Pathogenic Mechanism of Der p 38 as a Novel Allergen Homologous to RipA and RipB Proteins in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic relapsing pruritic disease encompassing skin inflammation and barrier dysfunction. House dust mites are key allergens that augment the development of atopic dermatitis. We aimed to investigate the pathogenic mechanism of AD due to Der p 38, recently identified by...

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Autores principales: Jeon, Hyang, Kim, Geunyeong, Kashif, Ayesha, Hong, Min Hwa, Lee, Ji-Sook, Hong, Yujin, Park, Beom Seok, Yang, Eun Ju, Kim, In Sik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531521/
https://www.ncbi.nlm.nih.gov/pubmed/34691014
http://dx.doi.org/10.3389/fimmu.2021.646316
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author Jeon, Hyang
Kim, Geunyeong
Kashif, Ayesha
Hong, Min Hwa
Lee, Ji-Sook
Hong, Yujin
Park, Beom Seok
Yang, Eun Ju
Kim, In Sik
author_facet Jeon, Hyang
Kim, Geunyeong
Kashif, Ayesha
Hong, Min Hwa
Lee, Ji-Sook
Hong, Yujin
Park, Beom Seok
Yang, Eun Ju
Kim, In Sik
author_sort Jeon, Hyang
collection PubMed
description Atopic dermatitis (AD) is a chronic relapsing pruritic disease encompassing skin inflammation and barrier dysfunction. House dust mites are key allergens that augment the development of atopic dermatitis. We aimed to investigate the pathogenic mechanism of AD due to Der p 38, recently identified by us. The frequency of IgE reactivity to Der p 38 in AD subjects was 52.6% (10/19) in the skin prick test and 57.9% (11/19) in the dot blot assay. In human keratinocyte HaCaT cells, Der p 38 triggered the impairment of filaggrin expression and induced pro-inflammatory cytokines such as IL-6, IL-8 and MCP-1 through TLR4, PI3K, AKT, c−Jun N−terminal kinase (JNK) and NF-κB pathway. Supernatants from Der p 38-treated cells blocked filaggrin expression and neutrophil apoptosis. The anti-apoptotic effect of the Der p 38-released molecules on neutrophils was accomplished by inhibition of the caspase 9/3 pathway, and by increased MCL-1 expression and BCL-2/BAX expression ratio. In C57BL/6 wild type (WT) mice, Der p 38 induced a dose-dependent increase of AD-like skin lesions, with enhanced expressions of total and Der p 38-specific IgE. Der p 38 also diminished the expressions of skin barrier proteins and induced JNK activation. However, the AD-like features following cutaneous Der p 38 exposure were observed to be reduced in the TLR4 knockout (KO) group, as compared to the WT group. Skin infiltration of neutrophils, eosinophils and mast cells was increased in the WT mice, but was not portrayed in the TLR4 KO mice. These findings indicate that Der p 38 is a novel mite allergen that triggers AD by lowering skin barrier proteins and increasing inflammatory cells. Results of this study have thereby paved the way to unveil the pathogenic mechanisms of AD.
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spelling pubmed-85315212021-10-23 Pathogenic Mechanism of Der p 38 as a Novel Allergen Homologous to RipA and RipB Proteins in Atopic Dermatitis Jeon, Hyang Kim, Geunyeong Kashif, Ayesha Hong, Min Hwa Lee, Ji-Sook Hong, Yujin Park, Beom Seok Yang, Eun Ju Kim, In Sik Front Immunol Immunology Atopic dermatitis (AD) is a chronic relapsing pruritic disease encompassing skin inflammation and barrier dysfunction. House dust mites are key allergens that augment the development of atopic dermatitis. We aimed to investigate the pathogenic mechanism of AD due to Der p 38, recently identified by us. The frequency of IgE reactivity to Der p 38 in AD subjects was 52.6% (10/19) in the skin prick test and 57.9% (11/19) in the dot blot assay. In human keratinocyte HaCaT cells, Der p 38 triggered the impairment of filaggrin expression and induced pro-inflammatory cytokines such as IL-6, IL-8 and MCP-1 through TLR4, PI3K, AKT, c−Jun N−terminal kinase (JNK) and NF-κB pathway. Supernatants from Der p 38-treated cells blocked filaggrin expression and neutrophil apoptosis. The anti-apoptotic effect of the Der p 38-released molecules on neutrophils was accomplished by inhibition of the caspase 9/3 pathway, and by increased MCL-1 expression and BCL-2/BAX expression ratio. In C57BL/6 wild type (WT) mice, Der p 38 induced a dose-dependent increase of AD-like skin lesions, with enhanced expressions of total and Der p 38-specific IgE. Der p 38 also diminished the expressions of skin barrier proteins and induced JNK activation. However, the AD-like features following cutaneous Der p 38 exposure were observed to be reduced in the TLR4 knockout (KO) group, as compared to the WT group. Skin infiltration of neutrophils, eosinophils and mast cells was increased in the WT mice, but was not portrayed in the TLR4 KO mice. These findings indicate that Der p 38 is a novel mite allergen that triggers AD by lowering skin barrier proteins and increasing inflammatory cells. Results of this study have thereby paved the way to unveil the pathogenic mechanisms of AD. Frontiers Media S.A. 2021-10-08 /pmc/articles/PMC8531521/ /pubmed/34691014 http://dx.doi.org/10.3389/fimmu.2021.646316 Text en Copyright © 2021 Jeon, Kim, Kashif, Hong, Lee, Hong, Park, Yang and Kim 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
Jeon, Hyang
Kim, Geunyeong
Kashif, Ayesha
Hong, Min Hwa
Lee, Ji-Sook
Hong, Yujin
Park, Beom Seok
Yang, Eun Ju
Kim, In Sik
Pathogenic Mechanism of Der p 38 as a Novel Allergen Homologous to RipA and RipB Proteins in Atopic Dermatitis
title Pathogenic Mechanism of Der p 38 as a Novel Allergen Homologous to RipA and RipB Proteins in Atopic Dermatitis
title_full Pathogenic Mechanism of Der p 38 as a Novel Allergen Homologous to RipA and RipB Proteins in Atopic Dermatitis
title_fullStr Pathogenic Mechanism of Der p 38 as a Novel Allergen Homologous to RipA and RipB Proteins in Atopic Dermatitis
title_full_unstemmed Pathogenic Mechanism of Der p 38 as a Novel Allergen Homologous to RipA and RipB Proteins in Atopic Dermatitis
title_short Pathogenic Mechanism of Der p 38 as a Novel Allergen Homologous to RipA and RipB Proteins in Atopic Dermatitis
title_sort pathogenic mechanism of der p 38 as a novel allergen homologous to ripa and ripb proteins in atopic dermatitis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531521/
https://www.ncbi.nlm.nih.gov/pubmed/34691014
http://dx.doi.org/10.3389/fimmu.2021.646316
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