Endogenous IL-22 is dispensable for experimental glomerulonephritis

Area of Science:

• Immunology
• Nephrology
• Cytokine biology

Background:

• Interleukin-22 (IL-22) is crucial for immune regulation in barrier tissues.
• Its role in glomerular injury, a key kidney disease, remains unclear.
• Previous studies suggest IL-22's regenerative potential in renal tubular damage.

Purpose of the Study:

• To investigate the role of IL-22 in the immunopathogenesis of glomerular injury.
• To determine if IL-22 contributes to kidney damage in models of glomerulonephritis and glomerulosclerosis.

Main Methods:

• Assessed IL-22 receptor expression in kidney glomeruli.
• Measured IL-22 levels in mouse models of crescentic glomerulonephritis (cGN) and adriamycin-induced nephropathy.
• Utilized genetic deletion (IL-22 knockout) and antibody-mediated blockade of IL-22.
• Examined the impact of IL-22 deficiency in IL-22 binding protein knockout mice.

Main Results:

• IL-22 receptor is present in the glomerular compartment; IL-22 expression increases during cGN.
• γδ T cells and T_H17 cells are identified as primary IL-22 sources in nephritic kidneys.
• Genetic or antibody-mediated IL-22 deficiency did not alter disease severity in cGN or focal segmental glomerulosclerosis models.
• No significant phenotypic differences were observed in IL-22-deficient mice compared to wild-type controls.

Conclusions:

• Endogenous IL-22 plays a redundant role in experimental forms of glomerular injury.
• Alternative cytokine pathways, like IL-17A and IFN-γ, likely mediate glomerular damage.
• IL-22-targeted therapies may not be effective for treating kidney glomerular diseases.