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- Title
Metabolic reprogramming of alloantigen-activated T cells after hematopoietic cell transplantation.
- Authors
Nguyen, Hung D.; Chatterjee, Shilpak; Haarberg, Kelley M. K.; Yongxia Wu; Bastian, David; Heinrichs, Jessica; Jianing Fu; Daenthanasanmak, Anusara; Schutt, Steven; Shrestha, Sharad; Chen Liu; Honglin Wang; Hongbo Chi; Mehrotra, Shikhar; Xue-Zhong Yu; Wu, Yongxia; Fu, Jianing; Liu, Chen; Wang, Honglin; Chi, Hongbo
- Abstract
Alloreactive donor T cells are the driving force in the induction of graft-versus-host disease (GVHD), yet little is known about T cell metabolism in response to alloantigens after hematopoietic cell transplantation (HCT). Here, we have demonstrated that donor T cells undergo metabolic reprograming after allogeneic HCT. Specifically, we employed a murine allogeneic BM transplant model and determined that T cells switch from fatty acid β-oxidation (FAO) and pyruvate oxidation via the tricarboxylic (TCA) cycle to aerobic glycolysis, thereby increasing dependence upon glutaminolysis and the pentose phosphate pathway. Glycolysis was required for optimal function of alloantigen-activated T cells and induction of GVHD, as inhibition of glycolysis by targeting mTORC1 or 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) ameliorated GVHD mortality and morbidity. Together, our results indicate that donor T cells use glycolysis as the predominant metabolic process after allogeneic HCT and suggest that glycolysis has potential as a therapeutic target for the control of GVHD.
- Subjects
T cells; GRAFT versus host disease; HEMATOPOIETIC agents; CELL transplantation; FATTY acid oxidation
- Publication
Journal of Clinical Investigation, 2016, Vol 126, Issue 4, p1337
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI82587