{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:41:25Z","timestamp":1784853685034,"version":"3.55.0"},"reference-count":38,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":55,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["ZIA-HL-005102"],"award-info":[{"award-number":["ZIA-HL-005102"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,22]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Enhancing NAD\n                      <jats:sup>+<\/jats:sup>\n                      levels with nicotinamide riboside (NR) confers antiinflammatory effects in human disease, although immunoregulatory mechanisms remain poorly characterized. We previously showed that ex vivo NR supplementation of primary CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells from psoriatic individuals dampened immune responsiveness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>To validate this in vivo, we performed a randomized, placebo-controlled NR supplementation study in individuals with mild-to-moderate psoriasis. Participants received oral NR (500 mg twice daily) or matching placebo for 4 weeks, with blood samples collected at baseline and after supplementation. NR reduced Th17 immune responsiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Bulk CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell RNA-seq identified induction of the SLIT-ROBO signaling pathway. NR supplementation increased circulating SLIT2 levels and enhanced SLIT2 production in dermal fibroblasts. Pharmacologic and genetic interrogation in CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells and fibroblasts demonstrated that SLIT2, acting through the ROBO1 receptor, inhibited Rho GTPase signaling, thereby attenuating canonical Th17 polarization and fibroblast inflammatory activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      These findings indicate that NAD\n                      <jats:sup>+<\/jats:sup>\n                      augmentation exerts anti-inflammatory effects in psoriasis through SLIT2-ROBO1-mediated crosstalk between dermal fibroblasts and circulating CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells, leading to suppression of Th17-driven inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT04271735 (registration date \u2013 2020-08026), NCT01143454 (registration date - 2010-07-21), NCT01778569 (registration date \u2013 2013-01-22), and NCT00001846 (registration date \u2013 2001-01-11).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>The NHLBI Division of Intramural Research (HL005102 \u2013 MNS).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.203826","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:00:26Z","timestamp":1777392026000},"source":"Crossref","is-referenced-by-count":1,"title":["NAD+ augmentation by nicotinamide riboside engages SLIT2\/ROBO1 signaling to attenuate Th17 inflammation in psoriasis"],"prefix":"10.1172","volume":"11","author":[{"given":"Kim","family":"Han","sequence":"first","affiliation":[{"name":"Laboratory of Mitochondrial Biology and Metabolism, NHLBI,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael J.","family":"Klein","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Biology and Metabolism, NHLBI,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Recupero","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Biology and Metabolism, NHLBI,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Chiara","family":"Russo","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Biology and Metabolism, NHLBI,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Sharma","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Biology and Metabolism, NHLBI,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand K.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Biology and Metabolism, NHLBI,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Hassanzadeh","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Biology and Metabolism, NHLBI,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0029-8612","authenticated-orcid":true,"given":"Rebecca D.","family":"Huffstutler","sequence":"additional","affiliation":[{"name":"Cardiovascular Branch, NHLBI,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep K.","family":"Dagur","sequence":"additional","affiliation":[{"name":"Flow Cytometry Core Facility, NHLBI, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Fisk","sequence":"additional","affiliation":[{"name":"Integrated Data Science Section, NIAID, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam R.","family":"Redekar","sequence":"additional","affiliation":[{"name":"Integrated Data Science Section, NIAID, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-0000","authenticated-orcid":true,"given":"Michael N.","family":"Sack","sequence":"additional","affiliation":[{"name":"Laboratory of Mitochondrial Biology and Metabolism, NHLBI,"},{"name":"Cardiovascular Branch, NHLBI,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.04.003"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12091329"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-025-01394-0"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.117"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0216-6"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add5163"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39419-4"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.02.001"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI139828"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5897487"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi4862"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2300693"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101157"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI138538"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.07.043"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1106678"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-024-08997-1"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00530-X"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10080"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1224340"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-024-08991-7"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.7150\/jca.31877"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M500279-MCP200"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2467"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2017.27"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/cei\/uxad084"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13048"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.753477"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202301964"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445422"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00228"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2014.09.008"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1159\/000359974"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0186459"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf018"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-020-03572-9"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01020-z"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/203826\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T18:01:59Z","timestamp":1782064919000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/203826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,28]]},"references-count":38,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,5,5]]},"published-print":{"date-parts":[[2026,6,22]]}},"alternative-id":["10.1172\/jci.insight.203826"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.203826","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,28]]},"article-number":"e203826"}}