TY - JOUR
T1 - Unspecific CTL Killing Is Enhanced by High Glucose via TNF-Related Apoptosis-Inducing Ligand
AU - Yang, Wenjuan
AU - Denger, Andreas
AU - Diener, Caroline
AU - Küppers, Frederic
AU - Soriano-Baguet, Leticia
AU - Schäfer, Gertrud
AU - Yanamandra, Archana K.
AU - Zhao, Renping
AU - Knörck, Arne
AU - Schwarz, Eva C.
AU - Hart, Martin
AU - Lammert, Frank
AU - Roma, Leticia Prates
AU - Brenner, Dirk
AU - Christidis, Grigorios
AU - Helms, Volkhard
AU - Meese, Eckart
AU - Hoth, Markus
AU - Qu, Bin
N1 - Funding Information:
We thank the Institute for Clinical Hemostaseology and Transfusion Medicine for providing donor blood; Carmen H?ssig, Cora Hoxha, and Susanne Renno for excellent technical help; Xiangda Zhou for the support in HG-culture.
Publisher Copyright:
Copyright © 2022 Yang, Denger, Diener, Küppers, Soriano-Baguet, Schäfer, Yanamandra, Zhao, Knörck, Schwarz, Hart, Lammert, Roma, Brenner, Christidis, Helms, Meese, Hoth and Qu.
PY - 2022/2/21
Y1 - 2022/2/21
N2 - 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.
AB - 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.
KW - CTLs
KW - High glucose
KW - PI3K-Akt, NFκB
KW - ROS
KW - TRAIL
UR - http://www.scopus.com/inward/record.url?scp=85125864383&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/35265081
U2 - 10.3389/fimmu.2022.831680
DO - 10.3389/fimmu.2022.831680
M3 - Article
C2 - 35265081
AN - SCOPUS:85125864383
SN - 1664-3224
VL - 13
SP - 831680
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 831680
ER -