Journal
CELL METABOLISM
Volume 30, Issue 6, Pages 1055-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2019.10.004
Keywords
-
Categories
Funding
- Versus Arthritis [21386]
- British Heart Foundation [FS/12/38/29640]
- Queen Mary Innovation Ltd
- University of Birmingham
- Fondazione Cariplo [2015-0552]
- Cancer Research UK [C50242/A17728]
- Versus Arthritis Fellowship [21386]
- Institut Pasteur Foundation Cenci-Bolognetti
- Medical Research Council UK PhD studentship
- Oliver Bird PhD Studentship from the Nuffield Foundation
- Cancer Research UK Career Development fellowship [C50242/A17728]
- British Heart Foundation Intermediate Basic Science research fellowship [FS/12/38/29640]
- MRC [MR/K020250/1, G0800648, MR/N003063/1] Funding Source: UKRI
Ask authors/readers for more resources
Accumulation of lactate in the tissue microenvironment is a feature of both inflammatory disease and cancer. Here, we assess the response of immune cells to lactate in the context of chronic inflammation. We report that lactate accumulation in the inflamed tissue contributes to the upregulation of the lactate transporter SLC5A12 by human CD4(+) T cells. SLC5A12-mediated lactate uptake into CD4(+) T cells induces a reshaping of their effector phenotype, resulting in increased IL17 production via nuclear PKM2/STAT3 and enhanced fatty acid synthesis. It also leads to CD4(+) T cell retention in the inflamed tissue as a consequence of reduced glycolysis and enhanced fatty acid synthesis. Furthermore, antibody-mediated blockade of SLC5A12 ameliorates the disease severity in a murine model of arthritis. Finally, we propose that lactate/SLC5A12-induced metabolic reprogramming is a distinctive feature of lymphoid synovitis in rheumatoid arthritis patients and a potential therapeutic target in chronic inflammatory disorders.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available