Lactate induces metabolic and epigenetic reprogramming of pro-inflammatory Th17 cells.
Th17 cells
Tregs
histone lactylation
immunometabolism
lactate
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
06 12 2022
06 12 2022
Historique:
revised:
22
09
2022
received:
18
01
2022
accepted:
27
09
2022
pubmed:
11
10
2022
medline:
15
12
2022
entrez:
10
10
2022
Statut:
ppublish
Résumé
Increased lactate levels in the tissue microenvironment are a well-known feature of chronic inflammation. However, the role of lactate in regulating T cell function remains controversial. Here, we demonstrate that extracellular lactate predominantly induces deregulation of the Th17-specific gene expression program by modulating the metabolic and epigenetic status of Th17 cells. Following lactate treatment, Th17 cells significantly reduced their IL-17A production and upregulated Foxp3 expression through ROS-driven IL-2 secretion. Moreover, we observed increased levels of genome-wide histone H3K18 lactylation, a recently described marker for active chromatin in macrophages, in lactate-treated Th17 cells. In addition, we show that high lactate concentrations suppress Th17 pathogenicity during intestinal inflammation in mice. These results indicate that lactate is capable of reprogramming pro-inflammatory T cell phenotypes into regulatory T cells.
Identifiants
pubmed: 36215678
doi: 10.15252/embr.202254685
pmc: PMC9724659
doi:
Substances chimiques
Lactic Acid
33X04XA5AT
Banques de données
GEO
['GSE193358', 'GSE208727']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e54685Informations de copyright
© 2022 The Authors.
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