Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis
| العنوان: | Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis |
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| المؤلفون: | Sven R Quist, Philippe Grange, Matthieu Tihy, Lydia Deschamps, Bénédicte Oulès, Joe M. Segal, Giacomo Donati, Ana-Maria Cujba, Fiona M. Watt, Christina Philippeos, Matteo Vietri Rudan, Ken Natsuga, Nicolas Dupin |
| المصدر: | Nature Communications Nature Communications, Vol. 11, No 1 (2020) P. 5067 Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020) |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Keratinocytes, 0301 basic medicine, Cellular differentiation, Retinoic acid, General Physics and Astronomy, Acne Vulgaris/genetics/metabolism/pathology/physiopathology, Human skin, ddc:616.07, Interleukin-10/genetics/metabolism, B7-H1 Antigen, Pathogenesis, 030207 dermatology & venereal diseases, chemistry.chemical_compound, 0302 clinical medicine, GATA6 Transcription Factor, Acne Vulgaris, Homeostasis, lcsh:Science, Acne, Skin, Multidisciplinary, GATA6, integumentary system, Cell Differentiation, Interleukin-10, Humans, Sebaceous Glands, GATA6 Transcription Factor/genetics/metabolism, Skin/cytology/metabolism/pathology, Mechanisms of disease, medicine.anatomical_structure, Keratinocyte, endocrine system, Science, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, B7-H1 Antigen/genetics/metabolism, medicine, Sebaceous Glands/cytology/metabolism/pathology, business.industry, General Chemistry, medicine.disease, Keratinocytes/cytology/metabolism/pathology, 030104 developmental biology, chemistry, Immunology, lcsh:Q, business |
| الوصف: | Although acne is the most common human inflammatory skin disease, its pathogenic mechanisms remain incompletely understood. Here we show that GATA6, which is expressed in the upper pilosebaceous unit of normal human skin, is down-regulated in acne. GATA6 controls keratinocyte proliferation and differentiation to prevent hyperkeratinisation of the infundibulum, which is the primary pathological event in acne. When overexpressed in immortalised human sebocytes, GATA6 triggers a junctional zone and sebaceous differentiation program whilst limiting lipid production and cell proliferation. It modulates the immunological repertoire of sebocytes, notably by upregulating PD-L1 and IL10. GATA6 expression contributes to the therapeutic effect of retinoic acid, the main treatment for acne. In a human sebaceous organoid model GATA6-mediated down-regulation of the infundibular differentiation program is mediated by induction of TGFβ signalling. We conclude that GATA6 is involved in regulation of the upper pilosebaceous unit and may be an actionable target in the treatment of acne. Although acne vulgaris is the most common human inflammatory skin disease, its pathogenic mechanisms remain incompletely understood. Here the authors show that GATA6 is involved in maintaining homeostasis of the upper pilosebaceous unit of human skin and may contribute to acne pathogenesis. |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6634250ce907eec983e74be663e53234Test https://doi.org/10.1038/s41467-020-18784-zTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6634250ce907eec983e74be663e53234 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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