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| Home > Publications database > Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8+ T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness. > print |
| Home > Publications database > Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8+ T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness. > print |
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| 024 | 7 | _ | |a 10.1016/j.immuni.2019.03.005 |2 doi |
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| 100 | 1 | _ | |a Wu, Jingxia |0 P:(DE-He78)bf88e5f49a614f52ba8ce2cd433e6b41 |b 0 |e First author |
| 245 | _ | _ | |a Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8+ T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness. |
| 260 | _ | _ | |a New York, NY |c 2019 |b Elsevier |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a Patients with the neurological disorder HSAN-I suffer frequent infections, attributed to a lack of pain sensation and failure to seek care for minor injuries. Whether protective CD8+ T cells are affected in HSAN-I patients remains unknown. Here, we report that HSAN-I-associated mutations in serine palmitoyltransferase subunit SPTLC2 dampened human T cell responses. Antigen stimulation and inflammation induced SPTLC2 expression, and murine T-cell-specific ablation of Sptlc2 impaired antiviral-T-cell expansion and effector function. Sptlc2 deficiency reduced sphingolipid biosynthetic flux and led to prolonged activation of the mechanistic target of rapamycin complex 1 (mTORC1), endoplasmic reticulum (ER) stress, and CD8+ T cell death. Protective CD8+ T cell responses in HSAN-I patient PBMCs and Sptlc2-deficient mice were restored by supplementing with sphingolipids and pharmacologically inhibiting ER stress-induced cell death. Therefore, SPTLC2 underpins protective immunity by translating extracellular stimuli into intracellular anabolic signals and antagonizes ER stress to promote T cell metabolic fitness. |
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| 700 | 1 | _ | |a Sandhoff, Roger |0 P:(DE-He78)a928ded2085c8911822370cad0b4a728 |b 2 |e First author |
| 700 | 1 | _ | |a Ming, Yanan |b 3 |
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| 700 | 1 | _ | |a Timmerman, Vincent |b 5 |
| 700 | 1 | _ | |a Bonello-Palot, Nathalie |b 6 |
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| 700 | 1 | _ | |a Löscher, Wolfgang N |b 10 |
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| 773 | _ | _ | |a 10.1016/j.immuni.2019.03.005 |g Vol. 50, no. 5, p. 1218 - 1231.e5 |0 PERI:(DE-600)2001966-X |n 5 |p 1218 - 1231.e5 |t Immunity |v 50 |y 2019 |x 1074-7613 |
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