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@ARTICLE{Wu:143809,
      author       = {J. Wu$^*$ and S. Ma$^*$ and R. Sandhoff$^*$ and Y. Ming and
                      A. Hotz-Wagenblatt$^*$ and V. Timmerman and N. Bonello-Palot
                      and B. Schlotter-Weigel and M. Auer-Grumbach and P. Seeman
                      and W. N. Löscher and M. Reindl and F. Weiss and E. Mah and
                      N. Weisshaar$^*$ and A. Madi$^*$ and K. Mohr$^*$ and T.
                      Schlimbach$^*$ and R. M. Velasco Cárdenas$^*$ and J.
                      Koeppel$^*$ and F. Grünschläger$^*$ and L. Müller$^*$ and
                      M. Baumeister$^*$ and B. Brügger and M. Schmitt and G.
                      Wabnitz and Y. Samstag and G. Cui$^*$},
      title        = {{L}oss of {N}eurological {D}isease {HSAN}-{I}-{A}ssociated
                      {G}ene {SPTLC}2 {I}mpairs {CD}8+ {T} {C}ell {R}esponses to
                      {I}nfection by {I}nhibiting {T} {C}ell {M}etabolic
                      {F}itness.},
      journal      = {Immunity},
      volume       = {50},
      number       = {5},
      issn         = {1074-7613},
      address      = {New York, NY},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2019-01371},
      pages        = {1218 - 1231.e5},
      year         = {2019},
      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.},
      cin          = {D140 / D192 / A411 / G131},
      ddc          = {610},
      cid          = {I:(DE-He78)D140-20160331 / I:(DE-He78)D192-20160331 /
                      I:(DE-He78)A411-20160331 / I:(DE-He78)G131-20160331},
      pnm          = {314 - Tumor immunology (POF3-314)},
      pid          = {G:(DE-HGF)POF3-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30952607},
      doi          = {10.1016/j.immuni.2019.03.005},
      url          = {https://inrepo02.dkfz.de/record/143809},
}