Please use this identifier to cite or link to this item: doi:10.22028/D291-35120
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Title: High glucose enhances antigen-independent CTL killing via TRAIL
Author(s): Yang, Wenjuan
Denger, Andreas
Diener, Caroline
Küppers, Frederic
Soriano-Baguet, Leticia
Schäfer, Gertrud
Yanamandra, Archana K.
Zhao, Renping
Knörck, Arne
Schwarz, Eva C.
Hart, Martin
Lammert, Frank
Roma, Leticia Prates
Brenner, Dirk
Christidis, Grigorios
Helms, Volkhard
Meese, Eckart
Hoth, Markus
Qu, Bin
Language: English
Publisher/Platform: bioRxiv
Year of Publication: 2021
Publikation type: Other
Abstract: Cytotoxic T lymphocytes (CTLs) are involved in development of diabetes. However, the impact of excessive glucose on CTL-mediated antigen-independent killing remains elusive. Here, we report that TNF-related apoptosis inducing ligand (TRAIL) is substantially up- regulated in CTLs in environments with high glucose (HG) both in vitro and in vivo. The PI3K- Akt-NFκB axis and non-mitochondrial reactive oxygen species are essential in HG-induced TRAIL upregulation in CTLs. TRAILhigh CTLs induce apoptosis of pancreatic beta cell line 1.4E7. Metformin and Vitamin D synergistically reduce HG-enhanced expression of TRAIL in CTLs and coherently protect 1.4E7 cells from TRAIL-mediated apoptosis. Notably, in patients with diabetes, correlation between Vitamin D concentrations in plasma and glucose levels is linked to HG-enhanced TRAIL expression on CTLs. Microarray data reveal that OXCT2, an important enzyme in ketone body catabolism, is a promising target in response to vitamin D. Our work not only reveals a novel mechanism of CTL involvement in progression of diabetes, but also establishes CTLs as a target for combined metformin and vitamin D therapy to protect pancreatic beta cells of diabetic patients.
DOI of the first publication: 10.1101/2021.08.04.455060
URL of the first publication:
Link to this record: hdl:20.500.11880/32120
Date of registration: 4-Jan-2022
Notes: Preprint
Faculty: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Department: M - Biophysik
M - Humangenetik
M - Innere Medizin
NT - Biowissenschaften
Professorship: M - Prof. Dr. Markus Hoth
M - Prof. Dr. Frank Lammert
M - Prof. Dr. Eckhart Meese
NT - Prof. Dr. Volkhard Helms
Collections:Die Universitätsbibliographie

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