title: IKKα is involved in kidney recovery and regeneration of acute ischemia/reperfusion injury in mice through IL10-producing regulatory T cells.
abstract: The recovery phase after kidney ischemia/reperfusion (IR) injury is often associated with the suppression of inflammation and the proliferation of tubular epithelial cells (TECs). The duration of this phase is often determined by the suppression of inflammation and the proliferation of TECs. Several lines of evidence suggest that IκB kinase α (IKKα) not only promotes the production of anti-inflammatory factors and/or prevents the production of inflammatory factors, but also induces the accompanying cell differentiation and regeneration, and suppresses inflammation. We therefore hypothesized that IKKα could participate in the kidney repair after IR injury and have used a mouse model of acute kidney injury (AKI) to test this. We found that IKKα mediated the repair of the kidney via infiltrated regulatory T (Treg) cells, which can produce anti-inflammatory cytokine IL10, and that IKKα also increased the proliferation of the surviving TECs and suppressed of inflammation. In addition, the expression of indoleamine 2,3-dioxygenase (IDO) in TECs is consistent with the infiltration of IL10-producing Treg cells. We conclude that IKKα is involved in kidney recovery and regeneration through the Treg cells that can produce IL10, which might be a potential therapeutic target that can be used to promote kidney repair after IR injury.
authors.affiliation: Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wan
authors.affiliation: Division of Neurosurgery, Department of Surgery and Shanghai Neurosurgical Institute, The Second Military Medical University, Changzheng Hospital, Shanghai 200003, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Hou
authors.affiliation: Division of Nephrology, Department of Medicine, Affiliated Lianyungang Clinical Medical College of Nanjing Medical University, Lianyungang 222002, China.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China caochangchun@njmu.edu.cn.
authors.forename: Chang-Chun
authors.initials: CC
authors.lastname: Cao
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology; D005260:Female; D051550:I-kappa B Kinase / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D007684:Kidney Tubules / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D012038:Regeneration / Q000276:immunology / Q000502:physiology*; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*
chemical_list: C556062:IL10 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016328:NF-kappa B; D016753:Interleukin-10; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase
keywords: 3-dioxygenase; IL10; Indoleamine 2; Ischemia-reperfusion injury; IκB kinase α; Kidney; Repair; T regular cell