| Autor: |
Chen-Fang Lee, Ying-Chun Lo, Chih-Hsien Cheng, Georg J. Furtmüller, Byoungchol Oh, Vinicius Andrade-Oliveira, Ajit G. Thomas, Caitlyn E. Bowman, Barbara S. Slusher, Michael J. Wolfgang, Gerald Brandacher, Jonathan D. Powell |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 13, Iss 4, Pp 760-770 (2015) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2015.09.036 |
| Popis: |
Upon antigen recognition and co-stimulation, T lymphocytes upregulate the metabolic machinery necessary to proliferate and sustain effector function. This metabolic reprogramming in T cells regulates T cell activation and differentiation but is not just a consequence of antigen recognition. Although such metabolic reprogramming promotes the differentiation and function of T effector cells, the differentiation of regulatory T cells employs different metabolic reprogramming. Therefore, we hypothesized that inhibition of glycolysis and glutamine metabolism might prevent graft rejection by inhibiting effector generation and function and promoting regulatory T cell generation. We devised an anti-rejection regimen involving the glycolytic inhibitor 2-deoxyglucose (2-DG), the anti-type II diabetes drug metformin, and the inhibitor of glutamine metabolism 6-diazo-5-oxo-L-norleucine (DON). Using this triple-drug regimen, we were able to prevent or delay graft rejection in fully mismatched skin and heart allograft transplantation models. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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