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

  • 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. TRAIL<sup>high</sup> 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 TRAIL<sup>high</sup> CTLs might contribute to the destruction of pancreatic beta cells in a hyperglycemia condition.

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Document Type:Article
Author:Wenjuan Yang, Andreas DengerORCiD, Caroline DienerORCiD, Frederic Küppers, Leticia Soriano-BaguetORCiD, Gertrud SchäferORCiD, Archana K. YanamandraORCiD, Renping ZhaoORCiD, Arne KnörckORCiD, Eva C. SchwarzORCiD, Martin Hart, Frank LammertORCiD, Leticia Prates RomaORCiD, Dirk BrennerORCiD, Grigorios ChristidisORCiD, Volkhard HelmsORCiD, Eckart MeeseORCiD, Markus HothORCiD, Bin QuORCiD
Parent Title (English):Frontiers in immunology
First Page:831680
Year of first Publication:2022
Release Date:2022/05/25
Impact:08.786 (2021)
Funding Information:Deutsche Forschungsgemeinschaft (SFB 1027 A2 to BQ, A11 to MHo, C3 and ZX to VH, TRR219 (M04) to LP), and HOMFOR2019 (to BQ). The flow cytometer was funded by DFG (GZ: INST 256/423-1 FUGG). LS-B and DB are funded by the FNR, respectively by the PRIDE program (PRIDE/11012546/NEXTIMMUNE) and the ATTRACT program (A14/BM/7632103).
Scientific Units:Fellow
Open Access:Open Access
Signature:INM 2022/035
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International