Multi-Antigen Imaging Reveals Inflammatory DC, ADAM17 and Neprilysin as Effectors in Keloid Formation
Keloid is an aberrant scarring process of the skin, characterized by excessive extracellular matrix synthesis and deposition. The pathogenesis of this prevalent cutaneous disorder is not fully understood; however, a persistent inflammatory process is observed. To obtain more insight into this proces...
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9417 |
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| author | Mathias Rath Alain Pitiot Michael Kirr Waltraud Fröhlich Bianca Plosnita Stefan Schliep Jürgen Bauerschmitz Andreas S. Baur Christian Ostalecki |
| author_facet | Mathias Rath Alain Pitiot Michael Kirr Waltraud Fröhlich Bianca Plosnita Stefan Schliep Jürgen Bauerschmitz Andreas S. Baur Christian Ostalecki |
| author_sort | Mathias Rath |
| collection | DOAJ |
| description | Keloid is an aberrant scarring process of the skin, characterized by excessive extracellular matrix synthesis and deposition. The pathogenesis of this prevalent cutaneous disorder is not fully understood; however, a persistent inflammatory process is observed. To obtain more insight into this process, we analyzed lesional, perilesional and healthy tissue using multi-antigen-analysis (MAA) in conjunction with a data mining approach. Here, we demonstrate that monocyte-derived inflammatory dendritic cells (CD1a+, CD11c+, CD14+) and activated CD4+ T lymphocytes (CD45 RO+) dominated the immune infiltration in keloids while associating with fibroblasts. In perilesional tissue, precursor immune cells were dominant in the perivascular area, suggesting that they were attracted by an immune process, potentially in the lesional area. Supporting this hypothesis, only in keloid lesions, high levels of ADAM10/17 and Neprilysin (CD10) were observed in both fibroblasts and leukocytes. The spatial proximity of these two cell types, which could be confirmed by image analysis only in lesional tissue, could be a potential factor leading to the activation of fibroblasts. Our findings provide new insight into the pathogenesis of keloid formation and reveal metalloproteinases as a target for therapeutical intervention. |
| first_indexed | 2024-03-10T08:10:53Z |
| format | Article |
| id | doaj.art-86fec926b78e4b6e984b8f8315bafc76 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:10:53Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-86fec926b78e4b6e984b8f8315bafc762023-11-22T10:43:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217941710.3390/ijms22179417Multi-Antigen Imaging Reveals Inflammatory DC, ADAM17 and Neprilysin as Effectors in Keloid FormationMathias Rath0Alain Pitiot1Michael Kirr2Waltraud Fröhlich3Bianca Plosnita4Stefan Schliep5Jürgen Bauerschmitz6Andreas S. Baur7Christian Ostalecki8Department of Urology, University Hospital Heidelberg, 69120 Heidelberg, GermanyLaboratory of Image & Data Analysis, Ilixa Ltd., London W1U 6NQ, UKDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, GermanyTissueGnostics GmbH, 1020 Vienna, AustriaDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, GermanyDepartment of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, GermanyKeloid is an aberrant scarring process of the skin, characterized by excessive extracellular matrix synthesis and deposition. The pathogenesis of this prevalent cutaneous disorder is not fully understood; however, a persistent inflammatory process is observed. To obtain more insight into this process, we analyzed lesional, perilesional and healthy tissue using multi-antigen-analysis (MAA) in conjunction with a data mining approach. Here, we demonstrate that monocyte-derived inflammatory dendritic cells (CD1a+, CD11c+, CD14+) and activated CD4+ T lymphocytes (CD45 RO+) dominated the immune infiltration in keloids while associating with fibroblasts. In perilesional tissue, precursor immune cells were dominant in the perivascular area, suggesting that they were attracted by an immune process, potentially in the lesional area. Supporting this hypothesis, only in keloid lesions, high levels of ADAM10/17 and Neprilysin (CD10) were observed in both fibroblasts and leukocytes. The spatial proximity of these two cell types, which could be confirmed by image analysis only in lesional tissue, could be a potential factor leading to the activation of fibroblasts. Our findings provide new insight into the pathogenesis of keloid formation and reveal metalloproteinases as a target for therapeutical intervention.https://www.mdpi.com/1422-0067/22/17/9417scardendritic cellstumor microenvironmentsingle-cell analysismultiplex imagingproteases |
| spellingShingle | Mathias Rath Alain Pitiot Michael Kirr Waltraud Fröhlich Bianca Plosnita Stefan Schliep Jürgen Bauerschmitz Andreas S. Baur Christian Ostalecki Multi-Antigen Imaging Reveals Inflammatory DC, ADAM17 and Neprilysin as Effectors in Keloid Formation International Journal of Molecular Sciences scar dendritic cells tumor microenvironment single-cell analysis multiplex imaging proteases |
| title | Multi-Antigen Imaging Reveals Inflammatory DC, ADAM17 and Neprilysin as Effectors in Keloid Formation |
| title_full | Multi-Antigen Imaging Reveals Inflammatory DC, ADAM17 and Neprilysin as Effectors in Keloid Formation |
| title_fullStr | Multi-Antigen Imaging Reveals Inflammatory DC, ADAM17 and Neprilysin as Effectors in Keloid Formation |
| title_full_unstemmed | Multi-Antigen Imaging Reveals Inflammatory DC, ADAM17 and Neprilysin as Effectors in Keloid Formation |
| title_short | Multi-Antigen Imaging Reveals Inflammatory DC, ADAM17 and Neprilysin as Effectors in Keloid Formation |
| title_sort | multi antigen imaging reveals inflammatory dc adam17 and neprilysin as effectors in keloid formation |
| topic | scar dendritic cells tumor microenvironment single-cell analysis multiplex imaging proteases |
| url | https://www.mdpi.com/1422-0067/22/17/9417 |
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