Generation of CD8+ memory Tcells requires metabolic reprogramming that is characterized by enhanced mitochondrial fatty-acid oxidation (FAO). However, where the fatty acids (FA) that fuel this process come from remains unclear. While CD8+ memory Tcells engage FAO to a greater extent, we found that they acquired substantially fewer long-chain FA from their external environment than CD8+ effector T (Teff) cells. Rather than using extracellular FA directly, memory Tcells used extracellular glucose to support FAO and oxidative phosphorylation (OXPHOS), suggesting that lipids must be synthesized to generate the substrates needed for FAO. We have demonstrated that memory Tcells rely on cell intrinsic expression of the lysosomal hydrolase LAL (lysosomal acid lipase) to mobilize FA for FAO and memory Tcell development. Our observations link LAL to metabolic reprogramming in lymphocytes and show that cell intrinsic lipolysis is deterministic for memory Tcell fate.
|Number of pages||14|
|State||Published - Jul 17 2014|