ResearchIn-Press PreviewDermatologyInflammation Open Access | 10.1172/jci.insight.151846
1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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1Department of Dermatology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
2Department of Dermatology, Medical Faculty, Heinrich-Heine-University, Dusseldorf, Germany
3Department of Genetics, Université Paris Descartes, Sorbonne Paris-Cité, INSERM U781, Paris, France
4Department of Angiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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Published January 12, 2023 - More info
Rosacea is a common chronic inflammatory skin disease with a fluctuating course of excessive inflammation and apparent neovascularization. Microbial dysbiosis with high density of B. oleronius and increased activity of kallikrein 5, which cleaves cathelicidin antimicrobial peptide, are key pathogenic triggers in rosacea. However, how these events are linked to the disease remains unknown. Here, we show that type I interferons produced by plasmacytoid dendritic cells represent the pivotal link between dysbiosis, the aberrant immune response, and neovascularization. Compared to other commensal bacteria, B. oleronius is highly susceptible and preferentially killed by cathelicidin antimicrobial peptides leading to enhanced generation of complexes with bacterial DNA. These bacterial DNA-complexes but not DNA-complexes derived from host cells are required for cathelicidin-induced activation of plasmacytoid dendritic cells and type I interferon production. Moreover, kallikrein 5 cleaves cathelicidin into peptides with heightened DNA-binding and type I interferon-inducing capacities. In turn, excessive type I interferon expression drives neoangiogenesis via IL22 induction and upregulation of the IL22 receptor on endothelial cells. These findings unravel a novel pathomechanism, which directly links hallmarks of rosacea to the killing of dysbiotic commensal bacteria with induction of a pathogenic type I interferon-driven and IL22-mediated angiogenesis.