PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis.
Systemic sclerosis (SSc) is a chronic autoimmune disorder that can result in extensive tissue damage in the skin and, in advanced cases, internal organs. Vasculopathy, aberrant immune activation, and tissue fibrosis are three hallmarks of the disease that have been identified, with vasculopathy and...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5019454?pdf=render |
| _version_ | 1818607522462826496 |
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| author | John S Cho Terry C Fang Taylor L Reynolds Daniel J Sofia Stefan Hamann Linda C Burkly |
| author_facet | John S Cho Terry C Fang Taylor L Reynolds Daniel J Sofia Stefan Hamann Linda C Burkly |
| author_sort | John S Cho |
| collection | DOAJ |
| description | Systemic sclerosis (SSc) is a chronic autoimmune disorder that can result in extensive tissue damage in the skin and, in advanced cases, internal organs. Vasculopathy, aberrant immune activation, and tissue fibrosis are three hallmarks of the disease that have been identified, with vasculopathy and aberrant immunity being amongst the earliest events. However, a mechanistic link between these processes has not been established. Here, we have identified a novel role of platelet derived growth factor-BB (PDGF-BB)/PDGFRβ activation in combination with dermal injury induced by bleomycin as a driver of early, aberrant expression of interferon stimulatory genes (ISGs) and inflammatory monocyte infiltration. Activation of PDGFRβ in combination with bleomycin-induced dermal injury resulted in increased dermal thickness, vascular density, monocyte/macrophage infiltration, and exacerbation of tissue injury. Many of these features were dependent on IFNAR-signaling, and an increase in the number of interferon-beta (IFN-β) producing monocytes cells was found in the skin lesions. Taken together, these results identify a novel link between PDGFRβ activation, and Type I IFN-driven vascular maintenance and monocyte/macrophage cell recruitment, and provide a potential explanation linking key features of SSc that were previously thought to be unrelated. |
| first_indexed | 2024-12-16T14:28:05Z |
| format | Article |
| id | doaj.art-ef8fcb24ed5343cb98d3a81aea22dc82 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T14:28:05Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ef8fcb24ed5343cb98d3a81aea22dc822022-12-21T22:28:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016275810.1371/journal.pone.0162758PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis.John S ChoTerry C FangTaylor L ReynoldsDaniel J SofiaStefan HamannLinda C BurklySystemic sclerosis (SSc) is a chronic autoimmune disorder that can result in extensive tissue damage in the skin and, in advanced cases, internal organs. Vasculopathy, aberrant immune activation, and tissue fibrosis are three hallmarks of the disease that have been identified, with vasculopathy and aberrant immunity being amongst the earliest events. However, a mechanistic link between these processes has not been established. Here, we have identified a novel role of platelet derived growth factor-BB (PDGF-BB)/PDGFRβ activation in combination with dermal injury induced by bleomycin as a driver of early, aberrant expression of interferon stimulatory genes (ISGs) and inflammatory monocyte infiltration. Activation of PDGFRβ in combination with bleomycin-induced dermal injury resulted in increased dermal thickness, vascular density, monocyte/macrophage infiltration, and exacerbation of tissue injury. Many of these features were dependent on IFNAR-signaling, and an increase in the number of interferon-beta (IFN-β) producing monocytes cells was found in the skin lesions. Taken together, these results identify a novel link between PDGFRβ activation, and Type I IFN-driven vascular maintenance and monocyte/macrophage cell recruitment, and provide a potential explanation linking key features of SSc that were previously thought to be unrelated.http://europepmc.org/articles/PMC5019454?pdf=render |
| spellingShingle | John S Cho Terry C Fang Taylor L Reynolds Daniel J Sofia Stefan Hamann Linda C Burkly PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis. PLoS ONE |
| title | PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis. |
| title_full | PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis. |
| title_fullStr | PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis. |
| title_full_unstemmed | PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis. |
| title_short | PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis. |
| title_sort | pdgf bb promotes type i ifn dependent vascular alterations and monocyte recruitment in a model of dermal fibrosis |
| url | http://europepmc.org/articles/PMC5019454?pdf=render |
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