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

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

Journal: Frontiers in immunology 2022;13():831680

PMID: 35265081

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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 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.

Address: Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany.; Center for Bioinformatics, Saarland University, Saarbrücken, Germany.; Institute of Human Genetics, School of Medicine, Saarland University, Homburg, Germany.; Internal Medicine II, University Hospital Saarland, Homburg, Germany.; Experimental and Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.; Immunology and Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg.; Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.; INM-Leibniz Institute for New Materials, Saarbrücken, Germany.; Hannover Medical School (MHH), Hannover, Germany.; Odense Research Center for Anaphylaxis, Department of Dermatology and Allergy Center, Odense University Hospital University of Southern Denmark, Odense, Denmark.

DOI: 10.3389/fimmu.2022.831680

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MeSH Terms: Glucose, Phosphatidylinositol 3-Kinases, Receptors, TNF-Related Apoptosis-Inducing Ligand, T-Lymphocytes, Cytotoxic, TNF-Related Apoptosis-Inducing Ligand