Frontiers in Immunology (Feb 2022)

Unspecific CTL Killing Is Enhanced by High Glucose via TNF-Related Apoptosis-Inducing Ligand

  • Wenjuan Yang,
  • Andreas Denger,
  • Caroline Diener,
  • Frederic Küppers,
  • Leticia Soriano-Baguet,
  • Leticia Soriano-Baguet,
  • Leticia Soriano-Baguet,
  • Gertrud Schäfer,
  • Archana K. Yanamandra,
  • Archana K. Yanamandra,
  • Renping Zhao,
  • Arne Knörck,
  • Eva C. Schwarz,
  • Martin Hart,
  • Frank Lammert,
  • Frank Lammert,
  • Leticia Prates Roma,
  • Dirk Brenner,
  • Dirk Brenner,
  • Dirk Brenner,
  • Grigorios Christidis,
  • Volkhard Helms,
  • Eckart Meese,
  • Markus Hoth,
  • Bin Qu,
  • Bin Qu

DOI
https://doi.org/10.3389/fimmu.2022.831680
Journal volume & issue
Vol. 13

Abstract

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TNF-related apoptosis inducing ligand (TRAIL) is expressed on cytotoxic T lymphocytes (CTLs) and TRAIL is linked to progression of diabetes. However, the impact of high glucose on TRAIL expression and its related killing function in CTLs still remains largely elusive. Here, we report that TRAIL is substantially up-regulated in CTLs in environments with high glucose (HG) both in vitro and in vivo. Non-mitochondrial reactive oxygen species, NFκB and PI3K/Akt are essential in HG-induced TRAIL upregulation in CTLs. TRAILhigh CTLs induce apoptosis of pancreatic beta cell line 1.4E7. Treatment with metformin and vitamin D reduces HG-enhanced expression of TRAIL in CTLs and coherently protects 1.4E7 cells from TRAIL-mediated apoptosis. Our work suggests that HG-induced TRAILhigh CTLs might contribute to the destruction of pancreatic beta cells in a hyperglycemia condition.

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