Abstract: TH-PO272

CC-Chemokine Receptor 7 Deficient Mice Are Resistant to Renal Ischemia Reperfusion Injury

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Kojima, Hiroshi, National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
  • Hu, Xuzhen, National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
  • Koritzinsky, Erik H., National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
  • Kim, Myung-gyu, National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
  • Street, Jonathan, National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
  • Break, Timothy J, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, Maryland, United States
  • Lionakis, Michail, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, Maryland, United States
  • Yuen, Peter S.T., National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
  • Star, Robert A., National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), 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 Dendritic Cells (DCs) to T cells areas of lymphoid tissues where T cells priming occur. Apart from chemotaxis, CCR7 controls cytoarchitecture, rate of endocytosis, survival, migratory speed, and maturation of the DCs. Manipulation of 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

CCR7 deficient mice (CCR7-/-) or wild-type mice (CCR7+/+) underwent IRI. Mice were euthanized at 1, 3 and 7 days after the surgery. Kidney & serum were collected for biochemical analysis & histological evaluation.

Results

Blood urea nitrogen, cystatin C, & creatinine levels in CCR7-/- were lower than CCR7+/+ throughout experimental periods. Similarly, CCR7-/- developed milder tubulointerstitial injuries than CCR7+/+. There was a significant correlation between serum markers & histology score.

Conclusion

CCR7-/- mice are resistant to IRI. We speculate that dendritic cells (DCs) are involved the reno-protective property in CCR7-/-. In CCR7+/+, IR induced danger signals induce normal maturation/activation of DCs, causing the development of effector T cell response. In CCR7-/-, DC maturation is prevented; DCs would remain in the state of immune tolerance despite the presence of danger signals.
Implications: Targeting DCs through CCR7 may have therapeutic potential for IRI.

Funding

  • NIDDK Support