Date: Monday, May 1, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 3:42pm-3:54pm
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 November 23, 2020.
« Back to 2017 American Transplant Congress