A novel renoprotective strategy: Upregulation of pd-l1 mitigates cisplatin-induced acute kidney injury

Jun Liu, David C. Yang, Jun Zhang, Ssu Wei Hsu, Robert H Weiss, Ching Hsien Chen

Research output: Contribution to journalArticlepeer-review

Abstract

The innate and adaptive immunities have been documented to participate in the pathogen-esis of nephrotoxic acute kidney injury (AKI); however, the mechanisms controlling these processes have yet to be established. In our cisplatin-induced AKI mouse model, we show pathological damage to the kidneys, with the classical markers elevated, consistent with the response to cisplatin treat-ment. Through assessments of the components of the immune system, both locally and globally, we demonstrate that the immune microenvironment of injured kidneys was associated with an increased infiltration of CD4+ T cells and macrophages concomitant with decreased Treg cell populations. Our cell-based assays and animal studies further show that cisplatin exposure downregulated the protein levels of programmed death-ligand 1 (PD-L1), an immune checkpoint protein, in primary renal proximal tubular epithelial cells, and that these inhibitions were dose-dependent. After or-thotopic delivery of PD-L1 gene into the kidneys, cisplatin-exposed mice displayed lower levels of both serum urea nitrogen and creatinine upon PD-L1 expression. Our data suggest a renoprotec-tive effect of the immune checkpoint protein, and thereby provide a novel therapeutic strategy for cisplatin-induced AKI.

Original languageEnglish (US)
Article number13304
JournalInternational journal of molecular sciences
Volume22
Issue number24
DOIs
StatePublished - Dec 1 2021

Keywords

  • AKI
  • Immune checkpoint
  • Inflammation
  • Renal tubules
  • T cells

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'A novel renoprotective strategy: Upregulation of pd-l1 mitigates cisplatin-induced acute kidney injury'. Together they form a unique fingerprint.

Cite this