Lactate induces metabolic and epigenetic reprogramming of pro-inflammatory Th17 cells

EMBO Rep. 2022 Dec 6;23(12):e54685. doi: 10.15252/embr.202254685. Epub 2022 Oct 10.


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.

Keywords: Th17 cells; Tregs; histone lactylation; immunometabolism; lactate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epigenomics
  • Lactic Acid*
  • Mice
  • Th17 Cells*


  • Lactic Acid

Associated data

  • GEO/GSE193358
  • GEO/GSE208727