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

Bénédicte Oulès, Christina Philippeos, Joe Segal, Matthieu Tihy, Matteo Vietri Rudan, Ana-Maria Cujba, Philippe A. Grange, Sven Quist, Ken Natsuga, Lydia Deschamps, Nicolas Dupin, Giacomo Donati and Fiona M. Watt ()
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Bénédicte Oulès: King’s College London
Christina Philippeos: King’s College London
Joe Segal: King’s College London
Matthieu Tihy: King’s College London
Matteo Vietri Rudan: King’s College London
Ana-Maria Cujba: King’s College London
Philippe A. Grange: Institut Cochin, Cutaneous Biology Lab, INSERM U1016, UMR8104
Sven Quist: Otto-von-Guericke-University
Ken Natsuga: Hokkaido University Graduate School of Medicine N15W7
Lydia Deschamps: Hôpitaux Universitaires Paris Nord Val de Seine
Nicolas Dupin: Institut Cochin, Cutaneous Biology Lab, INSERM U1016, UMR8104
Giacomo Donati: University of Turin
Fiona M. Watt: King’s College London

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18784-z

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