Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy

Front Immunol. 2024 Jan 15:14:1335936. doi: 10.3389/fimmu.2023.1335936. eCollection 2023.

Abstract

The glomerular filtration barrier, comprising the inner layer of capillary fenestrated endothelial cells, outermost podocytes, and the glomerular basement membrane between them, plays a pivotal role in kidney function. Podocytes, terminally differentiated epithelial cells, are challenging to regenerate once injured. They are essential for maintaining the integrity of the glomerular filtration barrier. Damage to podocytes, resulting from intrinsic or extrinsic factors, leads to proteinuria in the early stages and eventually progresses to chronic kidney disease (CKD). Immune-mediated podocyte injury is a primary pathogenic mechanism in proteinuric glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and lupus nephritis with podocyte involvement. An extensive body of evidence indicates that podocytes not only contribute significantly to the maintenance of the glomerular filtration barrier and serve as targets of immune responses but also exhibit immune cell-like characteristics, participating in both innate and adaptive immunity. They play a pivotal role in mediating glomerular injury and represent potential therapeutic targets for CKD. This review aims to systematically elucidate the mechanisms of podocyte immune injury in various podocyte lesions and provide an overview of recent advances in podocyte immunotherapy. It offers valuable insights for a deeper understanding of the role of podocytes in proteinuric glomerular diseases, and the identification of new therapeutic targets, and has significant implications for the future clinical diagnosis and treatment of podocyte-related disorders.

Keywords: immunity response; pathogenesis; podocyte; proteinuria; treatment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endothelial Cells / pathology
  • Glomerular Basement Membrane / pathology
  • Humans
  • Immunity
  • Podocytes* / pathology
  • Renal Insufficiency, Chronic* / drug therapy
  • Renal Insufficiency, Chronic* / therapy

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by a grant from the Central government guide local science and technology development special fund project: Xinjiang kidney disease big data smart medical innovation research and application base construction (grant number ZYYD2022C18) to CL. It was also supported by the Tianshan Talents - High-level Leading Talents Project (Department of Science and Technology of Xinjiang Uygur Autonomous Region): Construction and expansion of precision diagnosis and treatment system of chronic kidney disease based on clinical pathway and DRG (grant number 2022TSYCLJ0022) to CL.