The promise of immune cell therapy for acute kidney injury
Hamid Rabb
Hamid Rabb
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Commentary

The promise of immune cell therapy for acute kidney injury

Abstract

Acute kidney injury (AKI) often results from ischemia reperfusion, sepsis, or exposure to nephrotoxins and is associated with a high rate of mortality and morbidity. Advances in understanding the pathophysiology of AKI may lead to the development of specific therapies. Although there is evidence of an important role for immune cells in AKI, the specific relevant populations and the mechanisms of their actions are unclear. In this issue of the JCI, Li et al. demonstrate that adenosine manipulates DC responses to kidney injury, raising hope that immunotherapy could be a tangible approach to AKI.

Authors

Hamid Rabb

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Figure 1

Immune cells in AKI.

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Immune cells in AKI. Immune cells likely mediate AKI while in circulatio...
Immune cells likely mediate AKI while in circulation and when localized in the renal microvasculature, renal interstitium, and lymphoid tissue. While in the renal microcirculation during reperfusion, these cells increase their adhesiveness and adhere to activated endothelium and other cells, accentuating the “plug” that contributes to the no-reflow phenomenon. Some immune cells migrate into the interstitium, but there are also well-described resident renal immune cells. T and B cell, DC, NK and NKT cell, macrophage, and neutrophil crosstalk accentuates the postischemic inflammation. These cells produce and respond to cytokines, chemokines, oxygen free radicals, complement, coagulant factors, and other mediators. Adenosine, acting via A2AR, activates DCs, which in turn modulate NKT cell function by decreasing IFN-γ secretion. This triggers increased IL-10 levels, which subsequently downregulate postischemic inflammation. Panels depict the outer medulla. Adapted with permission from the Journal of Molecular Medicine (2).