Immunometabolic function of the transcription cofactor VGLL3 provides an evolutionary rationale for sexual dimorphism in autoimmunity.
Autoimmunity
Biological Evolution
Cell Death
/ drug effects
Chromatin
/ metabolism
Female
Humans
Inflammation
/ pathology
Interferon-alpha
/ pharmacology
Keratinocytes
/ immunology
Lupus Erythematosus, Systemic
/ immunology
Male
Nutritional Physiological Phenomena
Sex Characteristics
Signal Transduction
/ drug effects
Skin
/ pathology
Stress, Physiological
Transcription Factors
/ immunology
Tumor Suppressor Protein p53
/ metabolism
autoimmunity
immunometabolism
sexual dimorphism
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
25
03
2020
revised:
13
07
2020
accepted:
10
08
2020
pubmed:
18
8
2020
medline:
13
5
2021
entrez:
18
8
2020
Statut:
ppublish
Résumé
Sexual dimorphism is exhibited remarkably in the female predominance of autoimmune diseases (e.g. systemic lupus erythematosus, female-to-male ratio 9 : 1). To understand the female bias in autoimmunity, we focused on vestigial-like family member 3 (VGLL3), a molecule with increased expression in females and known to promote autoimmunity. We report that VGLL3 mediates the cellular stress response by upregulating p53 and IL-17C. Energy stress allows VGLL3 to be induced by IFNα, which ultimately leads to p53-dependent, lupus-associated, inflammatory cell death. Our results suggest that female-biased expression of VGLL3 helps cells adapt to metabolic stress, which, intriguingly, is known as a significant challenge during the evolution of placental mammals due to the need to feed a developing embryo. The findings also uncover the importance of maintaining metabolic homeostasis in the prevention of autoimmunity.
Identifiants
pubmed: 32803756
doi: 10.1002/1873-3468.13911
pmc: PMC7722229
mid: NIHMS1635367
doi:
Substances chimiques
Chromatin
0
Interferon-alpha
0
Transcription Factors
0
Tumor Suppressor Protein p53
0
VGLL3 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3371-3383Subventions
Organisme : NIAMS NIH HHS
ID : K01 AR073340
Pays : United States
Informations de copyright
© 2020 Federation of European Biochemical Societies.
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