Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8(+) T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F19%3A10394471" target="_blank" >RIV/00064203:_____/19:10394471 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/19:10394471
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=qB4ZFt6Jax" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=qB4ZFt6Jax</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.immuni.2019.03.005" target="_blank" >10.1016/j.immuni.2019.03.005</a>

Result language
angličtina
Original language name
Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8(+) T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness
Original language description
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 antiviralT-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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)

Project
<a href="/en/project/NV16-30206A" target="_blank" >NV16-30206A: Whole genome sequencing and RNA sequencing - a tool for elucidation of the causes of rare types of hereditary neuropathies.</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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