2. Academic Validation
  3. Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis

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

  • Nat Commun. 2020 Oct 20;11(1):5067. doi: 10.1038/s41467-020-18784-z.
Bénédicte Oulès 1 2 3,  Christina Philippeos 1,  Joe Segal 1 4,  Matthieu Tihy 1 5,  Matteo Vietri Rudan 1,  Ana-Maria Cujba 1,  Philippe A Grange 2 3,  Sven Quist 6,  Ken Natsuga 7,  Lydia Deschamps 8,  Nicolas Dupin 2 3,  Giacomo Donati 9,  Fiona M Watt 10
Affiliations

Affiliations

  • 1 Centre for Stem Cells and Regenerative Medicine, King's College London, Floor 28, Tower Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK.
  • 2 Université de Paris, Institut Cochin, Cutaneous Biology Lab, INSERM U1016, UMR8104, 24 rue du Faubourg St Jacques, 75014, Paris, France.
  • 3 Department of Dermatology, Hôpital Cochin, AP-HP, Groupe Hospitalier Paris Centre Cochin-Hôtel Dieu-Broca, 89 rue d'Assas, 75006, Paris, France.
  • 4 Division of Gastroenterology, University of California San Francisco Liver Center, 513 Parnassus Ave, HSE 1401, San Francisco, CA, 94143-1346, USA.
  • 5 Division of Clinical Pathology, University Hospitals of Geneva, Rue Michel-Servet 1, 1206, Genève, Switzerland.
  • 6 Clinic for Dermatology and Venerology, Otto-von-Guericke-University, Leipziger Straße 44, 39120, Magdeburg, Germany.
  • 7 Department of Dermatology, Hokkaido University Graduate School of Medicine N15W7, Sapporo, 060-8638, Japan.
  • 8 Department of Pathology, Hôpital Bichat, AP-HP, Hôpitaux Universitaires Paris Nord Val de Seine, 46 rue Henri Huchard, 75018, Paris, France.
  • 9 Department of Life Sciences and System Biology & Molecular Biotechnology Center, University of Turin, Turin, Italy.
  • 10 Centre for Stem Cells and Regenerative Medicine, King's College London, Floor 28, Tower Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK. fiona.watt@kcl.ac.uk.
PMID: 33082341 DOI: 10.1038/s41467-020-18784-z
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.

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