Abstract: FR-PO100
CC-Chemokine Receptor 7 Deficient Mice Are Resistant to Renal Ischemia-Reperfusion Injury
Session Information
- AKI: Mechanisms - Inflammation/Sepsis/Remote Injury
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Kojima, Hiroshi, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Koritzinsky, Erik H., NIDDK, NIH, Bethesda, Maryland, United States
- Kim, Myung-Gyu, NIDDK, NIH, Bethesda, Maryland, United States
- Street, Jonathan, NIDDK, NIH, Bethesda, Maryland, United States
- Break, Timothy, NIAID, NIH, Bethesda, Maryland, United States
- Lionakis, Michail, NIAID, NIH, Bethesda, Maryland, United States
- Yuen, Peter S.T., NIDDK, NIH, Bethesda, Maryland, United States
- Star, Robert A., NIDDK, NIH, Bethesda, Maryland, United States
Background
One of the most prominent chemokine receptors in the adaptive immune system is CC-chemokine receptor 7 (CCR7), which has been established as an important component of lymphocyte-driven immune function. CCR7 promotes homing of T cells and antigen presenting cells to areas of lymphoid tissues where T cell priming occurs. Apart from chemotaxis, CCR7 defines a precursor for natural killer T (NKT) cells in the thymus and periphery. Manipulation of the CCR7 axis has either protective or deleterious role in mouse kidney injury models. We sought to clarify the role of CCR7 in the pathogenesis of renal injury after ischemia reperfusion injury (IRI).
Methods
Experiment (Exp.) 1: CCR7 deficient mice (KO) or wild-type mice (WT) underwent IRI. Mice were euthanized at 1, 3 or 7 days after the surgery. Kidney & serum were collected for biochemical analysis & histological evaluation.
Exp. 2: KO or WT were injected intravenously with alpha-galactosylceramide: a specific ligand for NKT cells. NKT cells were isolated from spleen 24 hours later, and cytokine profiles were assessed by qPCR.
Exp. 3: Prior to IR surgery on Day 0, KO mice were injected intraperitoneally with IFNγ or vehicle on Days -3, -2, -1, and 0. Kidney & serum were harvested on Day 1.
Results
Exp. 1: Blood urea nitrogen & creatinine levels in KO were lower than WT throughout experimental periods. Similarly, KO developed milder tubulointerstitial injuries than WT.
Exp. 2: Serum IFNγ concentration & IFNγ mRNA expression in isolated NKT cells were lower in KO than WT.
Exp. 3: KO injected with IFNγ showed similar kidney damage to KO injected with vehicle.
Conclusion
CCR7 KO mice are resistant to IRI. KO mice show blunted production of IFNγ. We speculate that less production of IFNγ in KO induces insufficient development of an effector T cell response and reduces kidney damage. However, supplementation of IFNγ alone was not sufficient to increase the susceptibility to IRI in KO mice. Although we need further investigation to resolve the mechanism(s), intervention of CCR7 axis could have therapeutic potential for AKI, especially IRI.
Funding
- NIDDK Support