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Abstract: TH-OR074

Eosinophils-Mediated Protection Against Lupus Nephritis: Characterization of the Mechanisms and Demonstrating the Potential of IL-5 as a Novel Therapeutic Approach

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Liu, Ruihua, Sun Yat-sen University First Affiliated Hospital Department of Nephrology, Guangzhou, Guangdong, China
  • Mo, Xilong, Sun Yat-sen University First Affiliated Hospital Department of Nephrology, Guangzhou, Guangdong, China
  • Guo, Jing, Sun Yat-sen University First Affiliated Hospital Department of Nephrology, Guangzhou, Guangdong, China
  • Peng, Yuan, Sun Yat-sen University First Affiliated Hospital Department of Nephrology, Guangzhou, Guangdong, China
  • Wu, Haishan, Sun Yat-sen University First Affiliated Hospital Department of Nephrology, Guangzhou, Guangdong, China
  • Ye, Hongjian, Sun Yat-sen University First Affiliated Hospital Department of Nephrology, Guangzhou, Guangdong, China
  • Fan, Jinjin, Sun Yat-sen University First Affiliated Hospital Department of Nephrology, Guangzhou, Guangdong, China
  • Chen, Wei, Sun Yat-sen University First Affiliated Hospital Department of Nephrology, Guangzhou, Guangdong, China
  • Yang, Xiao, Sun Yat-sen University First Affiliated Hospital Department of Nephrology, Guangzhou, Guangdong, China
Background

Peripheral eosinophil counts are reduced in lupus nephritis and correlate with disease activity and adverse renal outcomes. This study aimed to investigate the role and therapeutic potential of eosinophils in the pathogenesis of lupus nephritis.

Methods

Peripheral eosinophil counts were analyzed in patients with lupus nephritis, IgA nephropathy, membranous nephropathy, other inflammatory nephropathies, and healthy controls. Eosinophil dynamics were tracked in the bone marrow, peripheral blood, spleen, and kidney of chronic graft-versus-host disease (cGVHD)-induced and MRL-lpr murine lupus models. Interventions included adoptive transfer of in vitro-derived eosinophils, eosinophil depletion—either through anti-IL-5 administration or using ΔdblGATA1 eosinophil-knockout mice, and IL-5 supplementation. Mechanistic analyses were performed by flow cytometry.

Results

Eosinophil counts were selectively reduced in patients with lupus nephritis. Murine models confirmed a systemic and renal eosinophil reduction during disease progression. Expansion of the eosinophil pool in vivo ameliorated lupus nephritis in the murine lupus models, whereas eosinophil depletion exacerbated disease progression. Decreased serum and renal levels IL-5 levels were observed in lupus-prone mice. Exogenous IL-5 administration restored eosinophil counts and mitigated disease severity, an effect associated with suppressed T cell-derived IL-17 production.

Conclusion

Eosinophils play a crucial protective role in lupus nephritis. Therapeutic strategies aimed at expanding eosinophils, particularly via IL-5 or its pegylated form, represent a promising novel approach for lupus nephritis treatment.

Acknowledgment

We sincerely thank members of our laboratory for their support. This work was supported by the Natural Science Foundation of China (Grant no. 82274277, 82074170), China Postdoctoral Science Foundation (Grant no. 2024M763764), the National Key Research and Development Project of China (Grant no. 2021YFC2501302), the Guangdong Provincial Key Laboratory of Nephrology (Grant no. 2020B1212060028) and NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University).

Funding

  • Government Support – Non-U.S.