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O’Sullivan, David; van der Windt, Gerritje J.W.; Huang, Stanley Ching-Cheng; Curtis, Jonathan D.; Chang, Chih-Hao; Buck, Michael D.; Qiu, Jing; Smith, Amber M.; Lam, Wing Y.; DiPlato, Lisa M.; Hsu, Fong-Fu; Birnbaum, Morris J.; Pearce, Edward J.; Pearce, Erika L.
Immunity, 07/2014, Letnik: 41, Številka: 1Journal Article
Generation of CD8+ memory T cells 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 T cells 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 T cells 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 T cells rely on cell intrinsic expression of the lysosomal hydrolase LAL (lysosomal acid lipase) to mobilize FA for FAO and memory T cell development. Our observations link LAL to metabolic reprogramming in lymphocytes and show that cell intrinsic lipolysis is deterministic for memory T cell fate. Display omitted •Unlike Teff cells, memory T cells do not acquire substantial amounts of long-chain FA•Glucose supports mitochondrial FAO and OXPHOS in memory T cells•Memory T cells use LAL-mediated cell-intrinsic lipolysis to mobilize FA for FAO•T cell-intrinsic lysosomal lipolysis is important for memory T cell development CD8+ memory T cells engage fatty-acid oxidation (FAO); however, the source of fatty acids that fuel FAO is unclear. O’Sullivan et al. show that memory T cells rely on glucose, and cell-intrinsic lipolysis to mobilize substrates, for FAO.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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