IL-22 promotes acute kidney injury through activation of the DNA damage response and cell death in proximal tubule cells.

Acute kidney injury, which affects 10-20% of hospitalized patients, is associated with a fourfold increase in mortality and predisposes patients to chronic kidney disease. In the present study, we identify interleukin 22 as a cofactor which worsens acute kidney injury. Interleukin 22 activates the DNA damage response, which in combination with nephrotoxic drugs amplifies the injury response in kidney epithelial cells and increases cell death. Deletion of interleukin 22 from mice or its receptor from mouse kidneys ameliorates cisplatin induced nephropathy. These findings may help clarify the molecular mechanisms of DNA damage induced kidney injury and identify interventions that can help treat acute kidney injury.