Lactate at the crossroads of metabolism, inflammation, and autoimmunity
Research output: Contribution to journal › Review article › peer-review
Colleges, School and Institutes
- William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M6BQ, UK.
For a long time after its discovery at the beginning of the 20th century, lactate was considered a waste product of cellular metabolism. Starting in the early ‘90s, however, lactate has begun to be recognized as an active molecule capable of modulating the immune response. Inflammatory sites, including in rheumatoid arthritis (RA) synovitis, are characterized by the accumulation of lactate, which is partly responsible for the establishment of an acidic environment. We have recently reported that T cells sense lactate via the expression of specific transporters, leading to inhibition of their motility. Importantly, this “stop migration signal” is dependent upon lactate's interference with intracellular metabolic pathways, specifically glycolysis. Furthermore, lactate promotes the switch of CD4+ T cells to an IL‐17+ subset, and reduces the cytolytic capacity of CD8+ T cells. These phenomena might be responsible for the formation of ectopic lymphoid structures and autoantibody production in inflammatory sites such as in RA synovitis, Sjogren syndrome salivary glands, and multiple sclerosis plaques. Here, we review the roles of lactate in the modulation of the inflammatory immune response.
|Number of pages||8|
|Journal||European Journal of Immunology|
|Early online date||24 Nov 2016|
|Publication status||Published - 1 Jan 2017|
- Arthritis, Inflammation, Lactate, Metabolism, T cells