Dendritic Cell Expression of Rictor (mTORC2), but Not Raptor (mTORC1), Protects Against Renal Ischemia-Reperfusion Injury.
1Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA
2Westmead Institute for Medical Research, Sydney, Australia
3Urologic Organ Transplantation Department, the Second Xiangya Hospital, Central South University, Changsha, China
Meeting: 2017 American Transplant Congress
Abstract number: 218
Keywords: knockout, Mice, Renal ischemia, Warm ischemia
Session Information
Session Name: Concurrent Session: Emerging Interventions in Ischemia Reperfusion Injury
Session Type: Concurrent Session
Date: Monday, May 1, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 3:42pm-3:54pm
Location: E351
Background: Dendritic cells (DC) are critical initiators of innate immunity in the kidney and orchestrate inflammation subsequent to ischemia-reperfusion injury (IRI). The mechanistic target of rapamycin (mTOR) is a kinase that functions as 2 independent complexes, mTOR complex 1 (Raptor) and complex 2 (Rictor). The role of mTOR in renal IRI pathophysiology has been poorly characterized, although the influence of DC-based alterations in mTOR signalling have not been investigated.
Methods:CD11c-specific Raptor-/- or Rictor-/- mice were generated by crossing respective floxed mice with B6 mice expressing CD11c-Cre. The genetic background of crossed mice was verified by PCR genotyping. Age- and gender-matched null mice or littermate controls underwent bilateral renal IRI and 24 h reperfusion, followed by assessment of renal function, histopathology and biomolecular analysis.
Results: CD11c-Raptor-/- mice demonstrated no difference in renal function compared to control mice. However, CD11c-Rictor-/- mice displayed significantly worse renal function and histologic damage compared to littermate controls (creatinine: 1.2±0.1 vs 0.8±0.1mg/dl respectively, p< 0.05; score of tubular damage: 4.1±0.2 vs 2.8±0.6 respectively; p<0.05). Deterioration in renal function also reflected a worsening pro-inflammatory cytokine profile (TNFα, IL-1β), with only renal-specific increases in DC, macrophage (CD11b+F4/80+) and T cell infiltrates. Renal Rictor-/- DC also demonstrated enhanced cell surface costimulatory CD40 and CD86 and decreased inhibitory PD-L1 molecule expression post-IRI.
Conclusion: These novel data show that DC-targeted elimination of Rictor promotes renal IRI, highlighting the regulatory role of both DC and mTOR complex 2 in the pathophysiology of acute kidney injury.
CITATION INFORMATION: Dai H, Rogers N, Watson A, Fantus D, Thomson A. Dendritic Cell Expression of Rictor (mTORC2), but Not Raptor (mTORC1), Protects Against Renal Ischemia-Reperfusion Injury. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Dai H, Rogers N, Watson A, Fantus D, Thomson A. Dendritic Cell Expression of Rictor (mTORC2), but Not Raptor (mTORC1), Protects Against Renal Ischemia-Reperfusion Injury. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/dendritic-cell-expression-of-rictor-mtorc2-but-not-raptor-mtorc1-protects-against-renal-ischemia-reperfusion-injury/. Accessed May 13, 2025.« Back to 2017 American Transplant Congress