| First Author | Lee CF | Year | 2015 |
| Journal | Cell Rep | Volume | 13 |
| Issue | 4 | Pages | 760-770 |
| PubMed ID | 26489460 | Mgi Jnum | J:277944 |
| Mgi Id | MGI:6274162 | Doi | 10.1016/j.celrep.2015.09.036 |
| Citation | Lee CF, et al. (2015) Preventing Allograft Rejection by Targeting Immune Metabolism. Cell Rep 13(4):760-770 |
| abstractText | 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. |
