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

Autor:	Yang W; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany., Denger A; Center for Bioinformatics, Saarland University, Saarbrücken, Germany., Diener C; Institute of Human Genetics, School of Medicine, Saarland University, Homburg, Germany., Küppers F; Internal Medicine II, University Hospital Saarland, Homburg, Germany., Soriano-Baguet L; 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., Schäfer G; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany., Yanamandra AK; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany.; INM-Leibniz Institute for New Materials, Saarbrücken, Germany., Zhao R; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany., Knörck A; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany., Schwarz EC; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany., Hart M; Institute of Human Genetics, School of Medicine, Saarland University, Homburg, Germany., Lammert F; Internal Medicine II, University Hospital Saarland, Homburg, Germany.; Hannover Medical School (MHH), Hannover, Germany., Roma LP; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany., Brenner D; 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.; Odense Research Center for Anaphylaxis, Department of Dermatology and Allergy Center, Odense University Hospital University of Southern Denmark, Odense, Denmark., Christidis G; Internal Medicine II, University Hospital Saarland, Homburg, Germany., Helms V; Center for Bioinformatics, Saarland University, Saarbrücken, Germany., Meese E; Institute of Human Genetics, School of Medicine, Saarland University, Homburg, Germany., Hoth M; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany., Qu B; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany.; INM-Leibniz Institute for New Materials, Saarbrücken, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Feb 21; Vol. 13, pp. 831680. Date of Electronic Publication: 2022 Feb 21 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.831680
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Yang, Denger, Diener, Küppers, Soriano-Baguet, Schäfer, Yanamandra, Zhao, Knörck, Schwarz, Hart, Lammert, Roma, Brenner, Christidis, Helms, Meese, Hoth and Qu.)
Databáze:	MEDLINE
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