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

Frontiers in Immunology

卷:13

Dirk Brenner¹  Leticia Prates Roma²  Eva C. Schwarz²  Wenjuan Yang²  Gertrud Schäfer²  Renping Zhao²  Arne Knörck²  Markus Hoth²  Volkhard Helms³  Andreas Denger³  Leticia Soriano-Baguet⁵  Frank Lammert⁶  Bin Qu⁷  Archana K. Yanamandra⁷  Eckart Meese⁹  Martin Hart⁹  Caroline Diener⁹  Frederic Küppers¹⁰  Grigorios Christidis¹⁰ 

[1] 0Odense Research Center for Anaphylaxis, Department of Dermatology and Allergy Center, Odense University Hospital University of Southern Denmark, Odense, Denmark;

[2] Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Homburg, Germany;

[3] Center for Bioinformatics, Saarland University, Saarbrücken, Germany;

[4] Experimental and Molecular Immunology, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg;

[5] Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg;

[6] Hannover Medical School (MHH), Hannover, Germany;

[7] INM-Leibniz Institute for New Materials, Saarbrücken, Germany;

[8] Immunology and Genetics, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Belvaux, Luxembourg;

[9] Institute of Human Genetics, School of Medicine, Saarland University, Homburg, Germany;

[10] Internal Medicine II, University Hospital Saarland, Homburg, Germany;

关键词: High glucose;    CTLs;    TRAIL;    ROS;    PI3K-Akt, NFκB;   

DOI  :  10.3389/fimmu.2022.831680

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown