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Keratinocyte-Immune Cell Crosstalk in a STAT1-Mediated Pathway: Novel Insights Into Rosacea Pathogenesis

Rosacea is a common chronic inflammatory condition that mainly affects the central face. However, the molecular background of the normal central face and the transcriptional profiling and immune cell composition of rosacea lesions remain largely unknown. Here, we performed whole-skin and epidermal R...

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Autores principales: Deng, Zhili, Liu, Fangfen, Chen, Mengting, Huang, Chuchu, Xiao, Wenqin, Gao, Sini, Jian, Dan, Ouyang, Yuyan, Xu, San, Li, Jinmao, Shi, Qian, Xie, Hongfu, Zhang, Guohong, Li, Ji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287635/
https://www.ncbi.nlm.nih.gov/pubmed/34290700
http://dx.doi.org/10.3389/fimmu.2021.674871
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author Deng, Zhili
Liu, Fangfen
Chen, Mengting
Huang, Chuchu
Xiao, Wenqin
Gao, Sini
Jian, Dan
Ouyang, Yuyan
Xu, San
Li, Jinmao
Shi, Qian
Xie, Hongfu
Zhang, Guohong
Li, Ji
author_facet Deng, Zhili
Liu, Fangfen
Chen, Mengting
Huang, Chuchu
Xiao, Wenqin
Gao, Sini
Jian, Dan
Ouyang, Yuyan
Xu, San
Li, Jinmao
Shi, Qian
Xie, Hongfu
Zhang, Guohong
Li, Ji
author_sort Deng, Zhili
collection PubMed
description Rosacea is a common chronic inflammatory condition that mainly affects the central face. However, the molecular background of the normal central face and the transcriptional profiling and immune cell composition of rosacea lesions remain largely unknown. Here, we performed whole-skin and epidermal RNA-seq of central facial skin from healthy individuals, lesions and matched normal skin from rosacea patients. From whole-skin RNA-seq, the site-specific gene signatures for central facial skin were mainly enriched in epithelial cell differentiation, with upregulation of the activator protein-1 (AP1) transcription factor (TF). We identified the common upregulated inflammatory signatures and diminished keratinization signature for rosacea lesions. Gene ontology, pathway, TF enrichment and immunohistochemistry results suggested that STAT1 was the potential core of the critical TF networks connecting the epithelial–immune crosstalk in rosacea lesions. Epidermal RNA-seq and immunohistochemistry analysis further validated the epithelial-derived STAT1 signature in rosacea lesions. The epidermal STAT1/IRF1 signature was observed across ETR, PPR, and PhR subtypes. Immune cell composition revealed that macrophages were common in all 3 subtypes. Finally, we described subtype-specific gene signatures and immune cell composition correlated with phenotypes. These findings reveal the specific epithelial differentiation in normal central facial skin, and epithelial–immune crosstalk in lesions providing insight into an initial keratinocyte pattern in the pathogenesis of rosacea.
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spelling pubmed-82876352021-07-20 Keratinocyte-Immune Cell Crosstalk in a STAT1-Mediated Pathway: Novel Insights Into Rosacea Pathogenesis Deng, Zhili Liu, Fangfen Chen, Mengting Huang, Chuchu Xiao, Wenqin Gao, Sini Jian, Dan Ouyang, Yuyan Xu, San Li, Jinmao Shi, Qian Xie, Hongfu Zhang, Guohong Li, Ji Front Immunol Immunology Rosacea is a common chronic inflammatory condition that mainly affects the central face. However, the molecular background of the normal central face and the transcriptional profiling and immune cell composition of rosacea lesions remain largely unknown. Here, we performed whole-skin and epidermal RNA-seq of central facial skin from healthy individuals, lesions and matched normal skin from rosacea patients. From whole-skin RNA-seq, the site-specific gene signatures for central facial skin were mainly enriched in epithelial cell differentiation, with upregulation of the activator protein-1 (AP1) transcription factor (TF). We identified the common upregulated inflammatory signatures and diminished keratinization signature for rosacea lesions. Gene ontology, pathway, TF enrichment and immunohistochemistry results suggested that STAT1 was the potential core of the critical TF networks connecting the epithelial–immune crosstalk in rosacea lesions. Epidermal RNA-seq and immunohistochemistry analysis further validated the epithelial-derived STAT1 signature in rosacea lesions. The epidermal STAT1/IRF1 signature was observed across ETR, PPR, and PhR subtypes. Immune cell composition revealed that macrophages were common in all 3 subtypes. Finally, we described subtype-specific gene signatures and immune cell composition correlated with phenotypes. These findings reveal the specific epithelial differentiation in normal central facial skin, and epithelial–immune crosstalk in lesions providing insight into an initial keratinocyte pattern in the pathogenesis of rosacea. Frontiers Media S.A. 2021-07-05 /pmc/articles/PMC8287635/ /pubmed/34290700 http://dx.doi.org/10.3389/fimmu.2021.674871 Text en Copyright © 2021 Deng, Liu, Chen, Huang, Xiao, Gao, Jian, Ouyang, Xu, Li, Shi, Xie, Zhang and Li 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
Deng, Zhili
Liu, Fangfen
Chen, Mengting
Huang, Chuchu
Xiao, Wenqin
Gao, Sini
Jian, Dan
Ouyang, Yuyan
Xu, San
Li, Jinmao
Shi, Qian
Xie, Hongfu
Zhang, Guohong
Li, Ji
Keratinocyte-Immune Cell Crosstalk in a STAT1-Mediated Pathway: Novel Insights Into Rosacea Pathogenesis
title Keratinocyte-Immune Cell Crosstalk in a STAT1-Mediated Pathway: Novel Insights Into Rosacea Pathogenesis
title_full Keratinocyte-Immune Cell Crosstalk in a STAT1-Mediated Pathway: Novel Insights Into Rosacea Pathogenesis
title_fullStr Keratinocyte-Immune Cell Crosstalk in a STAT1-Mediated Pathway: Novel Insights Into Rosacea Pathogenesis
title_full_unstemmed Keratinocyte-Immune Cell Crosstalk in a STAT1-Mediated Pathway: Novel Insights Into Rosacea Pathogenesis
title_short Keratinocyte-Immune Cell Crosstalk in a STAT1-Mediated Pathway: Novel Insights Into Rosacea Pathogenesis
title_sort keratinocyte-immune cell crosstalk in a stat1-mediated pathway: novel insights into rosacea pathogenesis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287635/
https://www.ncbi.nlm.nih.gov/pubmed/34290700
http://dx.doi.org/10.3389/fimmu.2021.674871
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