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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 s...

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Published in:Frontiers in immunology 2022-02, Vol.13, p.831680-831680
Main Authors: Yang, Wenjuan, Denger, Andreas, Diener, Caroline, Küppers, Frederic, Soriano-Baguet, Leticia, Schäfer, Gertrud, Yanamandra, Archana K, Zhao, Renping, Knörck, Arne, Schwarz, Eva C, Hart, Martin, Lammert, Frank, Roma, Leticia Prates, Brenner, Dirk, Christidis, Grigorios, Helms, Volkhard, Meese, Eckart, Hoth, Markus, Qu, Bin
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Language:English
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Summary: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 and . Non-mitochondrial reactive oxygen species, NFκB and PI3K/Akt are essential in HG-induced TRAIL upregulation in CTLs. TRAIL 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 CTLs might contribute to the destruction of pancreatic beta cells in a hyperglycemia condition.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.831680