Metabolic reprogramming of alloantigen-activated T cells after hematopoietic cell transplantation.
J Clin Invest
; 126(4): 1337-52, 2016 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-26950421
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 ß-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Transplante de Células-Tronco Hematopoéticas
/
Doença Enxerto-Hospedeiro
/
Isoantígenos
Limite:
Animals
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2016
Tipo de documento:
Article