[en] 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.
Disciplines :
Immunology & infectious disease
Author, co-author :
Yang, Wenjuan; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Denger, Andreas; Center for Bioinformatics, Saarland University, Saarbrücken, Germany
Diener, Caroline; Institute of Human Genetics, School of Medicine, Saarland University, Homburg, Germany
Küppers, Frederic; Internal Medicine II, University Hospital Saarland, Homburg, Germany
Soriano-Baguet, Leticia; 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, Gertrud; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Yanamandra, Archana K; 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, Renping; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Knörck, Arne; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Schwarz, Eva C; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Hart, Martin; Institute of Human Genetics, School of Medicine, Saarland University, Homburg, Germany
Lammert, Frank; Internal Medicine II, University Hospital Saarland, Homburg, Germany ; Hannover Medical School (MHH), Hannover, Germany
Roma, Leticia Prates; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
BRENNER, Dirk ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Immunology and Genetics ; Experimental and Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg ; Odense Research Center for Anaphylaxis, Department of Dermatology and Allergy Center, Odense University Hospital University of Southern Denmark, Odense, Denmark
Christidis, Grigorios; Internal Medicine II, University Hospital Saarland, Homburg, Germany
Helms, Volkhard; Center for Bioinformatics, Saarland University, Saarbrücken, Germany
Meese, Eckart; Institute of Human Genetics, School of Medicine, Saarland University, Homburg, Germany
Hoth, Markus; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany
Qu, Bin; Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany ; INM-Leibniz Institute for New Materials, Saarbrücken, Germany
Deutsche Forschungsgemeinschaft Fonds National de la Recherche Luxembourg
Funding text :
We thank the Institute for Clinical Hemostaseology and Transfusion Medicine for providing donor blood; Carmen Hässig, Cora Hoxha, and Susanne Renno for excellent technical help; Xiangda Zhou for the support in HG-culture.This project was funded by the Deutsche Forschungsgemeinschaft (SFB 1027 A2 to BQ, A11 to MHo, C3 and ZX to VH, TRR219 (M04) to LP), and HOMFOR2019 (to BQ). The flow cytometer was funded by DFG (GZ: INST 256/423-1 FUGG). LS-B and DB are funded by the FNR, respectively by the PRIDE program (PRIDE/11012546/NEXTIMMUNE) and the ATTRACT program (A14/BM/7632103).
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