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Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma
Systemic sclerosis (SSc), or scleroderma, is a multisystem autoimmune disorder characterized by vasculopathy and fibrosis in the skin and internal organs, most frequently in the esophagus and lungs. Hitherto, studies on SSc pathogenesis centered on immune cells, vascular cells, and fibroblasts. Alth...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379967/ https://www.ncbi.nlm.nih.gov/pubmed/28232470 http://dx.doi.org/10.1084/jem.20160247 |
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author | Takahashi, Takehiro Asano, Yoshihide Sugawara, Koji Yamashita, Takashi Nakamura, Kouki Saigusa, Ryosuke Ichimura, Yohei Toyama, Tetsuo Taniguchi, Takashi Akamata, Kaname Noda, Shinji Yoshizaki, Ayumi Tsuruta, Daisuke Trojanowska, Maria Sato, Shinichi |
author_facet | Takahashi, Takehiro Asano, Yoshihide Sugawara, Koji Yamashita, Takashi Nakamura, Kouki Saigusa, Ryosuke Ichimura, Yohei Toyama, Tetsuo Taniguchi, Takashi Akamata, Kaname Noda, Shinji Yoshizaki, Ayumi Tsuruta, Daisuke Trojanowska, Maria Sato, Shinichi |
author_sort | Takahashi, Takehiro |
collection | PubMed |
description | Systemic sclerosis (SSc), or scleroderma, is a multisystem autoimmune disorder characterized by vasculopathy and fibrosis in the skin and internal organs, most frequently in the esophagus and lungs. Hitherto, studies on SSc pathogenesis centered on immune cells, vascular cells, and fibroblasts. Although dysregulated keratinocytes in SSc have been recently reported, the contribution of epithelial cells to pathogenesis remains unexplored. In this study, we demonstrated the induction of SSc-like molecular phenotype in keratinocytes by gene silencing of transcription factor Friend leukemia virus integration 1 (Fli1), the deficiency of which is implicated in SSc pathogenesis. Keratin 14–expressing epithelial cell–specific Fli1 knockout mice spontaneously developed dermal and esophageal fibrosis with epithelial activation. Furthermore, they developed remarkable autoimmunity with interstitial lung disease derived from thymic defects with down-regulation of autoimmune regulator (Aire). Importantly, Fli1 directly regulated Aire expression in epithelial cells. Collectively, epithelial Fli1 deficiency might be involved in the systemic autoimmunity and selective organ fibrosis in SSc. This study uncovers unidentified roles of dysregulated epithelial cells in SSc pathogenesis. |
format | Online Article Text |
id | pubmed-5379967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53799672017-10-03 Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma Takahashi, Takehiro Asano, Yoshihide Sugawara, Koji Yamashita, Takashi Nakamura, Kouki Saigusa, Ryosuke Ichimura, Yohei Toyama, Tetsuo Taniguchi, Takashi Akamata, Kaname Noda, Shinji Yoshizaki, Ayumi Tsuruta, Daisuke Trojanowska, Maria Sato, Shinichi J Exp Med Research Articles Systemic sclerosis (SSc), or scleroderma, is a multisystem autoimmune disorder characterized by vasculopathy and fibrosis in the skin and internal organs, most frequently in the esophagus and lungs. Hitherto, studies on SSc pathogenesis centered on immune cells, vascular cells, and fibroblasts. Although dysregulated keratinocytes in SSc have been recently reported, the contribution of epithelial cells to pathogenesis remains unexplored. In this study, we demonstrated the induction of SSc-like molecular phenotype in keratinocytes by gene silencing of transcription factor Friend leukemia virus integration 1 (Fli1), the deficiency of which is implicated in SSc pathogenesis. Keratin 14–expressing epithelial cell–specific Fli1 knockout mice spontaneously developed dermal and esophageal fibrosis with epithelial activation. Furthermore, they developed remarkable autoimmunity with interstitial lung disease derived from thymic defects with down-regulation of autoimmune regulator (Aire). Importantly, Fli1 directly regulated Aire expression in epithelial cells. Collectively, epithelial Fli1 deficiency might be involved in the systemic autoimmunity and selective organ fibrosis in SSc. This study uncovers unidentified roles of dysregulated epithelial cells in SSc pathogenesis. The Rockefeller University Press 2017-04-03 /pmc/articles/PMC5379967/ /pubmed/28232470 http://dx.doi.org/10.1084/jem.20160247 Text en © 2017 Takahashi et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Takahashi, Takehiro Asano, Yoshihide Sugawara, Koji Yamashita, Takashi Nakamura, Kouki Saigusa, Ryosuke Ichimura, Yohei Toyama, Tetsuo Taniguchi, Takashi Akamata, Kaname Noda, Shinji Yoshizaki, Ayumi Tsuruta, Daisuke Trojanowska, Maria Sato, Shinichi Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma |
title | Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma |
title_full | Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma |
title_fullStr | Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma |
title_full_unstemmed | Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma |
title_short | Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma |
title_sort | epithelial fli1 deficiency drives systemic autoimmunity and fibrosis: possible roles in scleroderma |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379967/ https://www.ncbi.nlm.nih.gov/pubmed/28232470 http://dx.doi.org/10.1084/jem.20160247 |
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