en
Scientific article
Open access
English

Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis

Published inNature Communications, vol. 11, no. 1, 5067
Publication date2020
Abstract

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.

Keywords
  • Acne Vulgaris/genetics/metabolism/pathology/physiopathology
  • B7-H1 Antigen/genetics/metabolism
  • Cell Differentiation
  • GATA6 Transcription Factor/genetics/metabolism
  • Homeostasis
  • Humans
  • Interleukin-10/genetics/metabolism
  • Keratinocytes/cytology/metabolism/pathology
  • Sebaceous Glands/cytology/metabolism/pathology
  • Skin/cytology/metabolism/pathology
Citation (ISO format)
OULÈS, Bénédicte et al. Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis. In: Nature Communications, 2020, vol. 11, n° 1, p. 5067. doi: 10.1038/s41467-020-18784-z
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal2041-1723
328views
100downloads

Technical informations

Creation01/08/2021 4:25:00 PM
First validation01/08/2021 4:25:00 PM
Update time03/15/2023 11:52:38 PM
Status update03/15/2023 11:52:37 PM
Last indexation02/12/2024 12:00:41 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack