ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO099

Multifaceted Role of ST2/IL-33 Axis During Kidney Injury

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Sabapathy, Vikram, Division of Nephrology and CIIR, Charlottesville, Virginia, United States
  • Venkatadri, Rajkumar, Division of Nephrology and CIIR, Charlottesville, Virginia, United States
  • Dogan, Murat, Division of Nephrology and CIIR, Charlottesville, Virginia, United States
  • Mohammad, Saleh, Division of Nephrology and CIIR, Charlottesville, Virginia, United States
  • Cheru, Nardos Tesfaye, National Institutes of Health, Bethesda, Maryland, United States
  • Price, Airi, Division of Nephrology and CIIR, Charlottesville, Virginia, United States
  • Stevens, Brian K., Division of Nephrology and CIIR, Charlottesville, Virginia, United States
  • Sharma, Rahul, Division of Nephrology and CIIR, Charlottesville, Virginia, United States
Background

Renal diseases are a major cause of morbidity and mortality. Inflammation elicited by variety of cytokines and chemokines are a major player in initiation and progression of the disease. Interleukin 33 (IL-33) belongs to IL-1 family of cytokines, which was identified for eliciting T helper-2 (Th2) cytokines. IL-33 acts as an ‘alarmin’ that regulates the immune response during injury. IL-33 acts in an autocrine/paracrine manner on the ST2 membrane receptor IL33R or Il1rl1, triggering innate and adaptive immune response. ST2 is widely expressed in immune cells including regulatory T cells (Tregs). Importance of ST2/IL-33 signaling in Tregs has been demonstrated in multiple inflammatory conditions. However, cell specific contribution of ST2/IL33 signaling is not understood. Here, we investigated the cell specific ST2/IL33 signaling activity using murine renal injury models.

Methods

Murine ischemia-reperfusion injury (IRI) model was used to investigate cell specific ST2/IL-33 signaling using IL1RL1tm1a and cell specific Pepck, Foxd1 and Foxp3 -cre mice to delete ST2 expression in proximal tubular cells (PTC), pericytes and Tregs respectively. The structure and function of the kidney were probed using flow cytometry, histology, immunohistochemistry, qRT-PCR and biochemical analysis.

Results

In vivo experimental data indicated that deletion of ST2 in PTC and pericytes attenuated renal injury suggesting that activation of ST2/IL33 signaling in these cells leads to impaired renal function following IRI, leading to fibrosis. On the contrary, elimination of ST2/IL33 signaling from Tregs resulted in greater renal injury to the indicating that activation of ST2/IL33 signaling in Tregs mediate renal protection during inflammation and injury.

Conclusion

This study addresses the cell specific role of ST2/IL33 signaling in immune-regulation, fibrosis and repair. Our findings try to delineate the multifaceted role of ST2/IL33 axis in renal injury. We conclude modulation of ST2/IL33 siganling as a promising therapeutic option.

IL33/ST2 Signaling is a Double Edge Sword

Funding

  • NIDDK Support