{"doi":"10.1172/jci.insight.161318","title":"Immune checkpoint activity regulates polycystic kidney disease progression","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.","journal":"JCI Insight","year":2023,"id":338522,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9664,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":665767,"name":"Dustin T. Nguyen","orcid":null,"position":1,"is_corresponding":false},{"id":1071402,"name":"Kenneth H. Marsh","orcid":null,"position":2,"is_corresponding":false},{"id":676256,"name":"Colin Bauer","orcid":null,"position":3,"is_corresponding":false},{"id":1070984,"name":"Amy S. Li","orcid":"0000-0001-5304-8022","position":4,"is_corresponding":false},{"id":896192,"name":"Marie‐Louise T. Monaghan","orcid":"0000-0002-2907-3903","position":5,"is_corresponding":false},{"id":208557,"name":"Michael Berger","orcid":"0000-0002-3469-0076","position":6,"is_corresponding":false},{"id":978120,"name":"Seth B. Furgeson","orcid":"0009-0007-9530-8786","position":7,"is_corresponding":false},{"id":409881,"name":"Berenice Y. Gitomer","orcid":"0000-0002-7457-6497","position":8,"is_corresponding":false},{"id":335791,"name":"Michel B. Chonchol","orcid":null,"position":9,"is_corresponding":false},{"id":28343,"name":"Eric T. Clambey","orcid":"0000-0002-7972-9544","position":10,"is_corresponding":false},{"id":15661,"name":"Kurt A. Zimmerman","orcid":"0000-0003-1798-8046","position":11,"is_corresponding":false},{"id":32253,"name":"Raphael A. Nemenoff","orcid":"0000-0002-9051-814X","position":12,"is_corresponding":false},{"id":305250,"name":"Katharina Hopp","orcid":"0000-0002-2420-2358","position":13,"is_corresponding":false},{"id":267921,"name":"Emily K. Kleczko","orcid":"0000-0003-4254-5415","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T01:10:35.973121Z","pmid":"37345660","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}