Details

Autor(en) / Beteiligte

• Pucino, Valentina
• Bombardieri, Michele
• Pitzalis, Costantino
• Mauro, Claudio

Titel

Lactate at the crossroads of metabolism, inflammation, and autoimmunity

Ist Teil von

• European journal of immunology, 2017-01, Vol.47 (1), p.14-21

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek

Beschreibungen/Notizen

• 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. Lactate accumulates in the synovial joints during inflammation, and inhibits T‐cell motility by interfering with the glycolytic pathway. Loss of motility might be the cause of T‐cell entrapment in the synovial joint. Increased T‐cell retention and high local IL‐17 might in turn be responsible of the formation of ELSs.