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Dysregulated metabolism and immune cell function are key disease modifiers. The tryptophan metabolites, kynurenines, produced through indoleamine 2,3-dioxygenase 1 (IDO1), are known immunomodulators. Here, we study the role of tryptophan metabolism in PKD using an orthologous disease model (C57BL\/6J\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>RC\/RC<\/jats:sup>\n                    ). We found elevated kynurenine and IDO1 levels in\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>RC\/RC<\/jats:sup>\n                    kidneys versus wild type. Further, IDO1 levels were increased in ADPKD cell lines. Genetic\n                    <jats:italic>Ido1<\/jats:italic>\n                    loss in\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>RC\/RC<\/jats:sup>\n                    animals resulted in reduced PKD severity, as measured by cystic index and percentage kidney weight normalized to body weight. Consistent with an immunomodulatory role of kynurenines,\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>RC\/RC<\/jats:sup>\n                    ;\n                    <jats:italic>\n                      Ido1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice presented with significant changes in the cystic immune microenvironment (CME) versus controls. Kidney macrophage numbers decreased and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell numbers increased, both known PKD modulators. Also, pharmacological IDO1 inhibition in\n                    <jats:italic>Pkd1<\/jats:italic>\n                    <jats:sup>RC\/RC<\/jats:sup>\n                    mice and kidney-specific\n                    <jats:italic>Pkd2<\/jats:italic>\n                    -knockout mice with rapidly progressive PKD resulted in less severe PKD versus controls, with changes in the CME similar to those in the genetic model. Our data suggest that tryptophan metabolism is dysregulated in ADPKD and that its inhibition results in changes to the CME and slows disease progression, making IDO1 a therapeutic target for ADPKD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.154773","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T12:29:16Z","timestamp":1669292956000},"source":"Crossref","is-referenced-by-count":28,"title":["The tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase 1 regulates polycystic kidney disease progression"],"prefix":"10.1172","volume":"8","author":[{"given":"Dustin T.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Renal Diseases and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily K.","family":"Kleczko","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Renal Diseases and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Dwivedi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Renal Diseases and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Louise T.","family":"Monaghan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Renal Diseases and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice Y.","family":"Gitomer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Renal Diseases and Hypertension,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel B.","family":"Chonchol","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Renal Diseases and Hypertension,"},{"name":"Consortium for Fibrosis Research and Translation, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7972-9544","authenticated-orcid":true,"given":"Eric T.","family":"Clambey","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9051-814X","authenticated-orcid":true,"given":"Raphael A.","family":"Nemenoff","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Renal Diseases and Hypertension,"},{"name":"Consortium for Fibrosis Research and Translation, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Klawitter","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Renal Diseases and Hypertension,"},{"name":"Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2420-2358","authenticated-orcid":true,"given":"Katharina","family":"Hopp","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Renal Diseases and Hypertension,"},{"name":"Consortium for Fibrosis Research and Translation, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0047-y"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60601-1"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2014.05.020"},{"key":"B4","unstructured":"United States Renal Data System. 2018 USRDS Annual Data Report: Epidemiology of kidney disease in the United States. 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