IL-33 exacerbates acute kidney injury

Area of Science:

• Nephrology
• Immunology
• Inflammation research

Background:

• Inflammation is a key factor in acute kidney injury (AKI) pathogenesis.
• The role of the proinflammatory cytokine Interleukin-33 (IL-33) in AKI remains unclear.
• IL-33 protein expression increases in the kidney during cisplatin-induced AKI.

Purpose of the Study:

• To investigate the role of IL-33 in the development of acute kidney injury.
• To determine if IL-33 exacerbates kidney injury through CD4 T cell-mediated pathways.
• To explore the potential of targeting the IL-33/CXCL1 axis for AKI treatment.

Main Methods:

• Administered soluble ST2 (sST2) to neutralize IL-33 activity in cisplatin-induced AKI mouse models.
• Used recombinant IL-33 (rIL-33) to exacerbate AKI in wildtype and CD4-deficient mice.
• Assessed kidney injury markers including serum creatinine, acute tubular necrosis (ATN), apoptosis, and CD4 T cell infiltration.
• Measured chemokine CXCL1 levels in kidney tissue and evaluated the impact of CXCL1 receptor deficiency.

Main Results:

• Neutralization of IL-33 with sST2 reduced kidney inflammation, injury, and apoptosis in AKI mice.
• Recombinant IL-33 administration worsened AKI, increasing CD4 T cell infiltration and kidney damage.
• The injurious effects of IL-33 were dependent on CD4 T cells and the chemokine CXCL1.
• Mice lacking the CXCL1 receptor showed reduced AKI severity.

Conclusions:

• IL-33 promotes acute kidney injury by driving CD4 T cell production of CXCL1.
• Targeting IL-33 or CXCL1 presents a potential therapeutic avenue for managing AKI.