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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.
Immune cells in acute kidney injury
Acute kidney injury (AKI) occurs in 3%-7% of patients admitted to tertiary care hospitals in industrialized nations (1). In native kidneys, AKI-associated mortality approaches 50% when occurring in the intensive care unit, and AKI in allograft kidneys worsens short- and longterm kidney function. Ischemia/reperfusion injury (IRI) is a common cause, as are sepsis and nephrotoxins. There is no specific therapy except for supportive care and dialysis. While much of the initial work on AKI pathophysiology focused on the highly abundant epithelial cell, more recent studies have revealed an important role for immune, endothelial, and peritubular resident cells (2). The evidence for the role of immune cells emerged from studies showing that leukocyte adhesion molecules (LAMs) mediated AKI; however, many of the beneficial effects were independent of neutrophils being targeted by LAMs, which was initially confusing (3-5). Further studies demonstrated that ? cells were activated during AKI, migrated to kidney, and directly mediated tissue injury (6). This opened up the possibility of other immune populations such as DCs and NKT cells participating in AKI (ref. 7 and Figure 1). Work in other organs, such as lung, liver, and brain, has also revealed the engagement and participation of traditional immune cells in alloantigen-independent acute tissue injury (2, 8).
Adenosine receptor 2A agonistinduced tolerogenic DCs in AKI
Adenosine, a breakdown product of ATP/ ADP metabolism that accumulates in AKI, has been known to regulate lymphocyte responses and is thus an attractive target for modulating immune cells and improving outcomes in AKI (9). In the current issue of JCI, Li et al. have elegantly demonstrated that DCs can be modulated by adenosine or selective adenosine receptor agonists to...