Lactate exposure shapes the metabolic and transcriptomic profile of CD8+ T cells
| Autor: | Barbieri, Laura, Veliça, Pedro, Gameiro, Paulo A, Cunha, Pedro P, Foskolou, Iosifina P, Rullman, Eric, Bargiela, David, Johnson, Randall S, Rundqvist, Helene |
|---|---|
| Přispěvatelé: | Apollo - University of Cambridge Repository, Foskolou, Iosifina P [0000-0003-1874-6356] |
| Rok vydání: | 2023 |
| Předmět: | |
| Popis: | Funder: Wellcome Trust Funder: Cancer Research UK Funder: Medical Research Council INTRODUCTION: CD8+ T cells infiltrate virtually every tissue to find and destroy infected or mutated cells. They often traverse varying oxygen levels and nutrient-deprived microenvironments. High glycolytic activity in local tissues can result in significant exposure of cytotoxic T cells to the lactate metabolite. Lactate has been known to act as an immunosuppressor, at least in part due to its association with tissue acidosis. METHODS: To dissect the role of the lactate anion, independently of pH, we performed phenotypical and metabolic assays, high-throughput RNA sequencing, and mass spectrometry, on primary cultures of murine or human CD8+ T cells exposed to high doses of pH-neutral sodium lactate. RESULTS: The lactate anion is well tolerated by CD8+ T cells in pH neutral conditions. We describe how lactate is taken up by activated CD8+ T cells and can displace glucose as a carbon source. Activation in the presence of sodium lactate significantly alters the CD8+ T cell transcriptome, including the expression key effector differentiation markers such as granzyme B and interferon-gamma. DISCUSSION: Our studies reveal novel metabolic features of lactate utilization by activated CD8+ T cells, and highlight the importance of lactate in shaping the differentiation and activity of cytotoxic T cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|