Frontiers in Immunology (Feb 2022)
Unspecific CTL Killing Is Enhanced by High Glucose via TNF-Related Apoptosis-Inducing Ligand
- Wenjuan Yang,
- Andreas Denger,
- Caroline Diener,
- Frederic Küppers,
- Leticia Soriano-Baguet,
- Leticia Soriano-Baguet,
- Leticia Soriano-Baguet,
- Gertrud Schäfer,
- Archana K. Yanamandra,
- Archana K. Yanamandra,
- Renping Zhao,
- Arne Knörck,
- Eva C. Schwarz,
- Martin Hart,
- Frank Lammert,
- Frank Lammert,
- Leticia Prates Roma,
- Dirk Brenner,
- Dirk Brenner,
- Dirk Brenner,
- Grigorios Christidis,
- Volkhard Helms,
- Eckart Meese,
- Markus Hoth,
- Bin Qu,
- Bin Qu
Affiliations
- Wenjuan Yang
- Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
- Andreas Denger
- Center for Bioinformatics, Saarland University, Saarbrücken, Germany
- Caroline Diener
- Institute of Human Genetics, School of Medicine, Saarland University, Homburg, Germany
- Frederic Küppers
- Internal Medicine II, University Hospital Saarland, Homburg, Germany
- Leticia Soriano-Baguet
- Experimental and Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
- Leticia Soriano-Baguet
- Immunology and Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg
- Leticia Soriano-Baguet
- Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
- Gertrud Schäfer
- Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
- Archana K. Yanamandra
- Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
- Archana K. Yanamandra
- INM-Leibniz Institute for New Materials, Saarbrücken, Germany
- Renping Zhao
- Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
- Arne Knörck
- Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
- Eva C. Schwarz
- Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
- Martin Hart
- Institute of Human Genetics, School of Medicine, Saarland University, Homburg, Germany
- Frank Lammert
- Internal Medicine II, University Hospital Saarland, Homburg, Germany
- Frank Lammert
- Hannover Medical School (MHH), Hannover, Germany
- Leticia Prates Roma
- Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
- Dirk Brenner
- Experimental and Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
- Dirk Brenner
- Immunology and Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg
- Dirk Brenner
- 0Odense Research Center for Anaphylaxis, Department of Dermatology and Allergy Center, Odense University Hospital University of Southern Denmark, Odense, Denmark
- Grigorios Christidis
- Internal Medicine II, University Hospital Saarland, Homburg, Germany
- Volkhard Helms
- Center for Bioinformatics, Saarland University, Saarbrücken, Germany
- Eckart Meese
- Institute of Human Genetics, School of Medicine, Saarland University, Homburg, Germany
- Markus Hoth
- Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
- Bin Qu
- Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
- Bin Qu
- INM-Leibniz Institute for New Materials, Saarbrücken, Germany
- DOI
- https://doi.org/10.3389/fimmu.2022.831680
- Journal volume & issue
-
Vol. 13
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 in vitro and in vivo. Non-mitochondrial reactive oxygen species, NFκB and PI3K/Akt are essential in HG-induced TRAIL upregulation in CTLs. TRAILhigh 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 TRAILhigh CTLs might contribute to the destruction of pancreatic beta cells in a hyperglycemia condition.
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