{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:02:29Z","timestamp":1793325749790,"version":"4.5.0"},"reference-count":72,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["DK119375"],"award-info":[{"award-number":["DK119375"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["DK114164,DK114164-03S1"],"award-info":[{"award-number":["DK114164,DK114164-03S1"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["5T32DK007135"],"award-info":[{"award-number":["5T32DK007135"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001296","name":"PKD Foundation","doi-asserted-by":"crossref","award":["216G18a"],"award-info":[{"award-number":["216G18a"]}],"id":[{"id":"10.13039\/100001296","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Colorado, Anschutz Medical Campus, Consortium for Fibrosis Research and Translation","award":["Pilot"],"award-info":[{"award-number":["Pilot"]}]},{"name":"University of Colorado, Anschutz Medical Campus, Consortium for Fibrosis Research and Translation","award":["Feasibility Grant"],"award-info":[{"award-number":["Feasibility Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,22]]},"abstract":"<jats:p>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T cells and slow tumor growth. We have previously shown that in PKD, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell loss worsens disease. This study used orthologous early-onset and adult-onset ADPKD models (\n                    <jats:italic>Pkd1<\/jats:italic>\n                    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\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>RC\/RC<\/jats:sup>\n                    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\u2013PD-1 antibody did not impact PKD severity in early-onset or adult-onset ADPKD models. However, treatment with anti\u2013PD-1 plus anti\u2013CTLA-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\n                    <jats:sup>+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.161318","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T14:05:15Z","timestamp":1687356315000},"source":"Crossref","is-referenced-by-count":21,"title":["Immune checkpoint activity regulates polycystic kidney disease progression"],"prefix":"10.1172","volume":"8","author":[{"given":"Emily K.","family":"Kleczko","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Renal Diseases and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin T.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Renal Diseases and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth 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