Regulators of necroinflammation in acute kidney injury

Interleukin (IL)-22 is unique among the ILs as it elicits direct effects on kidney epithelia and regulates cell survival in a context-dependent manner. Studies published in Kidney International and other journals demonstrate opposing roles of IL-22 (e.g., in models of acute kidney injury). In the early necroinflammation phase of acute kidney injury, IL-22 promotes tubular cell death, whereas it enhances the proliferation and regeneration of epithelial barrier function in the healing phase of injured tubules. Interleukin (IL)-22 is unique among the ILs as it elicits direct effects on kidney epithelia and regulates cell survival in a context-dependent manner. Studies published in Kidney International and other journals demonstrate opposing roles of IL-22 (e.g., in models of acute kidney injury). In the early necroinflammation phase of acute kidney injury, IL-22 promotes tubular cell death, whereas it enhances the proliferation and regeneration of epithelial barrier function in the healing phase of injured tubules. IL-22 is secreted by proximal tubule cells and regulates DNA damage response and cell death in acute kidney injuryKidney InternationalVol. 105Issue 1PreviewAcute kidney injury (AKI) affects over 13 million people worldwide annually and is associated with a 4-fold increase in mortality. Our lab and others have shown that DNA damage response (DDR) governs the outcome of AKI in a bimodal manner. Activation of DDR sensor kinases protects against AKI, while hyperactivation of DDR effector proteins, such as p53, induces cell death and worsens AKI. The factors that trigger DDR to switch from pro-repair to pro-cell death remain to be resolved. Here we investigated the role of interleukin 22 (IL-22), an IL-10 family member whose receptor (IL-22RA1) is expressed on proximal tubule cells (PTCs), in DDR activation and AKI. Full-Text PDF