| |  Online-Ressource |
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| Verfasst von: | Wu, Jingxia [VerfasserIn]  |
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| | Ma, Sicong [VerfasserIn] |
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| | Sandhoff, Roger [VerfasserIn] |
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| | Ming, Yanan [VerfasserIn] |
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| | Hotz-Wagenblatt, Agnes [VerfasserIn] |
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| | Weisshaar, Nina [VerfasserIn] |
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| | Madi, Alaa [VerfasserIn] |
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| | Mohr, Kerstin [VerfasserIn] |
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| | Schlimbach, Tilo [VerfasserIn] |
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| | Velasco Cárdenas, Rubí Misol-Há [VerfasserIn] |
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| | Koeppel, Jonas [VerfasserIn] |
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| | Grünschläger, Florian [VerfasserIn] |
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| | Müller, Lisann [VerfasserIn] |
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| | Baumeister, Maren [VerfasserIn] |
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| | Brügger, Britta [VerfasserIn] |
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| | Schmitt, Michael [VerfasserIn] |
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| | Wabnitz, Guido H. [VerfasserIn] |
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| | Samstag, Yvonne [VerfasserIn] |
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| | Cui, Guoliang [VerfasserIn] |
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| Titel: | Loss of neurological disease HSAN-I-associated gene SPTLC2 impairs CD8+ T cell responses to infection by inhibiting T cell metabolic fitness |
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| Verf.angabe: | Jingxia Wu, Sicong Ma, Roger Sandhoff, Yanan Ming, Agnes Hotz-Wagenblatt, Vincent Timmerman, Nathalie Bonello-Palot, Beate Schlotter-Weigel, Michaela Auer-Grumbach, Pavel Seeman, Wolfgang N. Löscher, Markus Reindl, Florian Weiss, Eric Mah, Nina Weisshaar, Alaa Madi, Kerstin Mohr, Tilo Schlimbach, Rubí M. -H. Velasco Cárdenas, Jonas Koeppel, Florian Grünschläger, Lisann Müller, Maren Baumeister, Britta Brügger, Michael Schmitt, Guido Wabnitz, Yvonne Samstag, and Guoliang Cui |
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| E-Jahr: | 2019 |
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| Jahr: | 2 April 2019 |
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| Umfang: | 14 S. |
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| Fussnoten: | Gesehen am 18.12.2019 |
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| Titel Quelle: | Enthalten in: Immunity |
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| Ort Quelle: | [Cambridge, Mass.] : Cell Press, 1994 |
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| Jahr Quelle: | 2019 |
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| Band/Heft Quelle: | 50(2019), 5, Seite 1218-1231.e5 |
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| ISSN Quelle: | 1097-4180 |
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| Abstract: | 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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| DOI: | doi:10.1016/j.immuni.2019.03.005 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.immuni.2019.03.005 |
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| | Verlag: http://www.sciencedirect.com/science/article/pii/S1074761319300950 |
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| | DOI: https://doi.org/10.1016/j.immuni.2019.03.005 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | CD8+ T cells |
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| | ER stress |
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| | HSAN-I |
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| | neurological diseases |
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| | SPTLC2 |
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| K10plus-PPN: | 1685891608 |
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| Verknüpfungen: | → Zeitschrift |
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Loss of neurological disease HSAN-I-associated gene SPTLC2 impairs CD8+ T cell responses to infection by inhibiting T cell metabolic fitness / Wu, Jingxia [VerfasserIn]; 2 April 2019 (Online-Ressource)
