title: MicroRNA-23a Curbs Necrosis during Early T Cell Activation by Enforcing Intracellular Reactive Oxygen Species Equilibrium.
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.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Baojun
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Liu
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Chaoran
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Lykken
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wong
authors.affiliation: Institute of Cancer; Xinqiao Hospital; 400037; China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Biomedical Analysis Center; The Third Military Medical University; Chongqing; 400037; China.
authors.forename: Zhongfen
authors.initials: Z
authors.lastname: Tao
authors.affiliation: Institute of Cancer; Xinqiao Hospital; 400037; China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Biomedical Analysis Center; The Third Military Medical University; Chongqing; 400037; China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Qi-Jing
authors.initials: QJ
authors.lastname: Li
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism; D006706:Homeostasis; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008099:Liver / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009336:Necrosis; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C000631446:PPIF protein, mouse; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D011948:Receptors, Antigen, T-Cell; D021983:Cyclophilins