Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 10 2020
20 10 2020
Historique:
received:
18
03
2019
accepted:
14
09
2020
entrez:
21
10
2020
pubmed:
22
10
2020
medline:
25
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33082341
doi: 10.1038/s41467-020-18784-z
pii: 10.1038/s41467-020-18784-z
pmc: PMC7575575
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
GATA6 Transcription Factor
0
GATA6 protein, human
0
Interleukin-10
130068-27-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5067Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1100073
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 096540/Z/11/Z
Pays : United Kingdom
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