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 A_2AR, 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).