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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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Immunology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899024/
https://www.ncbi.nlm.nih.gov/pubmed/35265081
http://dx.doi.org/10.3389/fimmu.2022.831680
Descripción
Sumario: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(high) 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(high) CTLs might contribute to the destruction of pancreatic beta cells in a hyperglycemia condition.

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