MicroRNA-23a Curbs Necrosis during Early T Cell Activation by Enforcing Intracellular Reactive Oxygen Species Equilibrium.
Immunity
; 44(3): 568-581, 2016 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-26921109
ABSTRACT
Upon antigen engagement, augmented cytosolic reactive oxygen species (ROS) are needed to achieve optimal T cell receptor (TCR) signaling. However, uncontrolled ROS production is a prominent cause of necrosis, which elicits hyper-inflammation and tissue damage. Hence, it is critical to program activated T cells to achieve ROS equilibrium. Here, we determined that miR-23a is indispensable for effector CD4(+) T cell expansion, particularly by providing early protection from excessive necrosis. Mechanistically, miR-23a targeted PPIF, gatekeeper of the mitochondria permeability transition pore, thereby restricting ROS flux and maintaining mitochondrial integrity. Upon acute Listeria monocytogenes infection, deleting miR-23a in T cells resulted in excessive inflammation, massive liver damage, and a marked mortality increase, which highlights the essential role of miR-23a in maintaining immune homeostasis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
/
MicroRNAs
/
Listeriose
/
Listeria monocytogenes
/
Fígado
/
Mitocôndrias
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article