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, Gertrud Schäfer, Archana K. Yanamandra, Renping Zhao, Arne Knörck, Eva C. Schwarz, Martin Hart, Frank Lammert, Leticia Prates Roma, Dirk Brenner, Grigorios Christidis, Volkhard Helms, Eckart Meese, Markus Hoth, Bin Qu*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Article number831680
Pages (from-to)831680
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 21 Feb 2022

Keywords

  • CTLs
  • High glucose
  • PI3K-Akt, NFκB
  • ROS
  • TRAIL

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