PMID- 30190173
OWN - NLM
STAT- MEDLINE
DCOM- 20190705
LR  - 20191101
IS  - 1523-1755 (Electronic)
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 94
IP  - 5
DP  - 2018 Nov
TI  - Rictor deficiency in dendritic cells exacerbates acute kidney injury.
PG  - 951-963
LID - S0085-2538(18)30447-2 [pii]
LID - 10.1016/j.kint.2018.06.010 [doi]
AB  - Dendritic cells (DCs) are critical initiators of innate immunity in the kidney 
      and orchestrate inflammation following ischemia-reperfusion injury. The role of 
      the mammalian/mechanistic target of rapamycin (mTOR) in the pathophysiology of 
      renal ischemia-reperfusion injury has been characterized. However, the influence 
      of DC-based alterations in mTOR signaling is unknown. To address this, bone 
      marrow-derived mTORC2-deficient (Rictor(-/-)) DCs underwent hypoxia-reoxygenation 
      and then analysis by flow cytometry. Adoptive transfer of wild-type or 
      Rictor(-/-) DC to C57BL/6 mice followed by unilateral or bilateral renal 
      ischemia-reperfusion injury (20 min ischemia) was used to assess their in vivo 
      migratory capacity and influence on tissue injury. Age-matched male DC-specific 
      Rictor(-/-) mice or littermate controls underwent bilateral renal 
      ischemia-reperfusion, followed by assessment of renal function, histopathology, 
      and biomolecular and cell infiltration analysis. Rictor(-/-) DCs expressed more 
      costimulatory CD80/CD86 but less coinhibitory programmed death ligand 1 (PDL1), a 
      pattern that was enhanced by hypoxia-reoxygenation. They also demonstrated 
      enhanced migration to the injured kidney and induced greater tissue damage. 
      Following ischemia-reperfusion, Rictor(-/-) DC mice developed higher serum 
      creatinine levels, more severe histological damage, and greater proinflammatory 
      cytokine production compared to littermate controls. Additionally, a greater 
      influx of both neutrophils and T cells was seen in Rictor(-/-) DC mice, along 
      with CD11c(+)MHCII(+)CD11b(hi)F4/80(+) renal DC, that expressed more CD86 but 
      less PDL1. Thus, DC-targeted elimination of Rictor enhances inflammation and 
      migratory responses to the injured kidney, highlighting the regulatory roles of 
      both DCs and Rictor in the pathophysiology of acute kidney injury.
CI  - Copyright (c) 2018 International Society of Nephrology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Dai, Helong
AU  - Dai H
AD  - Department of Surgery, Thomas E. Starzl Transplantation Institute, University of 
      Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Department of 
      Urological Organ Transplantation, The Second Xiangya Hospital of Central South 
      University, Changsha, P.R. China.
FAU - Watson, Alicia R
AU  - Watson AR
AD  - Department of Surgery, Thomas E. Starzl Transplantation Institute, University of 
      Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Department of 
      Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 
      USA.
FAU - Fantus, Daniel
AU  - Fantus D
AD  - Department of Surgery, Thomas E. Starzl Transplantation Institute, University of 
      Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
FAU - Peng, Longkai
AU  - Peng L
AD  - Department of Urological Organ Transplantation, The Second Xiangya Hospital of 
      Central South University, Changsha, P.R. China.
FAU - Thomson, Angus W
AU  - Thomson AW
AD  - Department of Surgery, Thomas E. Starzl Transplantation Institute, University of 
      Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Department of 
      Immunology, University of Pittsburgh School of Medicine, Pittsburgh, 
      Pennsylvania, USA. Electronic address: thomsonaw@upmc.edu.
FAU - Rogers, Natasha M
AU  - Rogers NM
AD  - Department of Surgery, Thomas E. Starzl Transplantation Institute, University of 
      Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Center for 
      Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, 
      New South Wales, Australia; Westmead Clinical Medical School, University of 
      Sydney, Camperdown, New South Wales, Australia.
LA  - eng
GR  - R01 AI067541/AI/NIAID NIH HHS/United States
GR  - R56 AI118777/AI/NIAID NIH HHS/United States
GR  - T32 AI074490/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180904
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (B7-2 Antigen)
RN  - 0 (Cytokines)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
SB  - IM
MH  - Acute Kidney Injury/*etiology
MH  - Animals
MH  - B7-2 Antigen/analysis
MH  - Cytokines/genetics
MH  - Dendritic Cells/*physiology
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 2/deficiency/*physiology
MH  - Mice, Inbred C57BL
MH  - Neutrophil Infiltration
MH  - Signal Transduction/physiology
PMC - PMC6200603
MID - NIHMS990459
OTO - NOTNLM
OT  - Rictor
OT  - dendritic cells
OT  - kidney ischemia-reperfusion injury
COIS- DISCLOSURE All the authors declare no competing interests.
EDAT- 2018/09/08 06:00
MHDA- 2019/07/06 06:00
PMCR- 2019/11/01
CRDT- 2018/09/08 06:00
PHST- 2017/11/21 00:00 [received]
PHST- 2018/05/10 00:00 [revised]
PHST- 2018/06/07 00:00 [accepted]
PHST- 2018/09/08 06:00 [pubmed]
PHST- 2019/07/06 06:00 [medline]
PHST- 2018/09/08 06:00 [entrez]
PHST- 2019/11/01 00:00 [pmc-release]
AID - S0085-2538(18)30447-2 [pii]
AID - 10.1016/j.kint.2018.06.010 [doi]
PST - ppublish
SO  - Kidney Int. 2018 Nov;94(5):951-963. doi: 10.1016/j.kint.2018.06.010. Epub 2018 
      Sep 4.