ArticleJCI insight2023
Immune checkpoint activity regulates polycystic kidney disease progression.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- The Role of Immune Cells as Modulators of Progression in Polycystic Kidney Disease: A Systematic Review.Kidney360 · 2026Pooled it
- B7-1 and PD-L1 crosstalk in podocyte injury: from molecular mechanisms to novel therapeutic strategies for nephrotic syndrome.International urology and nephrology · 2026Review
- Toward Physiologically Relevant Organoid Models of Polycystic Kidney Disease through Microenvironment Reconstruction.Journal of the American Society of Nephrology : JASN · 2026Review
- TLR2 Activation Enhances Inflammatory Signaling and Accelerates Cyst Growth and Renal Fibrosis in Polycystic Kidney Disease Mice.International journal of molecular sciences · 2026Article
- Spatial Transcriptomics Reveals Injured Cells, Signature Genes, and Communication Patterns in the Cyst Microenvironment of Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2026Article
- Aldehyde dehydrogenase 1 A1 regulates the transcription of PD-L1 and its targeting with disulfiram together with PD-L1 immunotherapy synergistically delays cyst growth in ADPKD.Kidney international · 2026Article
- Immune microenvironment in autosomal dominant polycystic kidney disease.Genes & diseases · 2026Review
- Inhibition of the inflammasome ameliorates orthologous polycystic kidney disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A case of autosomal dominant polycystic kidney disease with systemic lupus erythematosus developing after SARS-CoV-2 vaccination.CEN case reports · 2025Article
- Antiproliferative effects of dihydrotanshinone I on autosomal dominant polycystic kidney disease via immunomodulation.The Journal of pharmacology and experimental therapeutics · 2025Article
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- Post-marketing safety concerns with Tislelizumab: a disproportionality analysis of the FDA adverse event reporting system.Frontiers in immunology · 2025Article
- Complement C3d enables cell-mediated immunity capable of distinguishing spontaneously transformed from nontransformed cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Immune-checkpoint inhibition to slow cyst growth.Nature reviews. Nephrology · 2023Article
- Deciphering Intercellular Communication of the Immune Landscape within Autosomal Dominant Polycystic Kidney Disease Microenvironment at Single-Cell Resolution.Kidney diseases (Basel, Switzerland)Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Innate and adaptive immune cells modulate the severity of autosomal dominant polycystic kidney disease (ADPKD), a common kidney disease with inadequate treatment options. ADPKD has parallels with cancer, in which immune checkpoint inhibitors have been shown to reactivate CD8+ T cells and slow tumor growth. We have previously shown that in PKD, CD8+ T cell loss worsens disease. This study used orthologous early-onset and adult-onset ADPKD models (Pkd1 p.R3277C) to evaluate the role of immune checkpoints in PKD. Flow cytometry of kidney cells showed increased levels of programmed cell death protein 1 (PD-1)/cytotoxic T lymphocyte associated protein 4 (CTLA-4) on T cells and programmed cell death ligand 1 (PD-L1)/CD80 on macrophages and epithelial cells in Pkd1RC/RC mice versus WT, paralleling disease severity. PD-L1/CD80 was also upregulated in ADPKD human cells and patient kidney tissue versus controls. Genetic PD-L1 loss or treatment with an anti-PD-1 antibody did not impact PKD severity in early-onset or adult-onset ADPKD models. However, treatment with anti-PD-1 plus anti-CTLA-4, blocking 2 immune checkpoints, improved PKD outcomes in adult-onset ADPKD mice; neither monotherapy altered PKD severity. Combination therapy resulted in increased kidney CD8+ T cell numbers/activation and decreased kidney regulatory T cell numbers correlative with PKD severity. Together, our data suggest that immune checkpoint activation is an important feature of and potential novel therapeutic target in ADPKD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.