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Abstract: SA-PO380

IL-9 Ameliorates Progressive Glomerulosclerosis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Xiong, Tingting, University Medical Center Hamburg, Hamburg, Germany
  • Attar, Madena, University Medical Center Hamburg, Hamburg, Germany
  • Becker, Martina, University Medical Center Hamburg, Hamburg, Germany
  • Turner, Jan-Eric, University Medical Center Hamburg, Hamburg, Germany

Group or Team Name

  • Turner Lab
Background

It has been established that IL-9 expression enhances tissue regeneration after lung injury, but data about the involvement of IL-9 in renal tissue protection are still very limited. Especially, the potential role of IL-9 in immune-mediated kidney disease is largely unknown. In this study, we focus on the role of IL-9 in Adriamycin-induced nephropathy (AN), a mouse model of focal and segmental glomerulosclerosis.

Methods

Progressive glomerulosclerosis in wild-type and Il9-/- mice was induced by injection of Adriamycin and analyses of histopathology, renal function parameters, albuminuria and renal immune cell infiltration were performed. The role of selective IL-9 deficiency of either the innate or the adaptive immune system for the outcome of AN was examined in Il9-/-Rag2-/- mice and IL-9deltaT,B mixed bone marrow chimeras, respectively. Il9Cre x R26reYFP fate reporter mice were used to assess the cellular source of IL-9 in AN.

Results

Il9-/- mice with AN displayed accelerated development of proteinuria, aggravated glomerulosclerosis and deterioration of kidney function, as compared to wild type (WT) mice. In line, electron microscopy revealed early aggravation of podocyte damage in Il9-/- mice. First experiments with IL-9 fate reporter mice suggested that T cells might be a major source of IL-9 in the injured kidney. Accordingly, innate IL-9 deficiency in Il9-/-Rag2-/- mice did not alter the outcome of AN, whereas selective deficiency of adaptive IL-9 in IL-9deltaT,B mixed bone marrow chimeras resulted in aggravation of glomerulosclerosis and kidney impairment, comparable to the phenotype observed in the completely IL-9-deficient mice. Possible mechanisms of the protective IL-9 effect, such as a direct pro-survival effect on glomerular epithelial or endothelial cells, are under active investigation.

Conclusion

In summary, we demonstrate here that IL-9 deficiency aggravates kidney failure in Adriamycin-induced nephropathy. As a cellular source of IL-9, T cells seem to play an important role in this model. The tissue-protective mechanisms of IL-9 need to be further elucidated and may offer a therapeutic approach in immune-mediated kidney diseases in the future.

Funding

  • Government Support - Non-U.S.