{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:55:03Z","timestamp":1785855303622,"version":"3.56.0"},"reference-count":59,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI161010"],"award-info":[{"award-number":["AI161010"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI162242"],"award-info":[{"award-number":["AI162242"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Liver\u2010resident natural killer (LrNK) cells are critical regulators of hepatic immune homeostasis and demonstrate antiviral activity, yet their role in lentivirus infections remains poorly defined. Using a rhesus macaque (RM) model of Simian immunodeficiency virus (SIV) and Simian\u2010human immunodeficiency virus (SHIV) infections, we investigated the phenotypes, metabolic profiles and functional responses of hepatic NK cells across na\u00efve, acutely SIV\u2010infected and chronically SHIV\u2010infected RM. We identified liver\u2010resident (Lr) NK cells as CD3\u2212CD159a\/c+CD49a+, whereas CD3\u2212CD159a\/c+CD49a\u2212 NK cells include circulating NK cell subsets in the liver. Across infection states, CD49a+ LrNK cells exhibited elevated expression of activation markers, including NKG2D, NKp30, NKp46 and CD69, as well as increased expression of metabolic markers, including CD98, Glut1 and MitoTracker. In contrast, Ki\u201067 expression was reduced in CD49a+ LrNK cells compared with their CD49a\u2212 counterparts. Unsupervised clustering revealed that CD49a+ LrNK cells were also marked by high CD69 expression. While total NK cell cytokine secretion was elevated in acute SIV\u2010infected animals, CD49a+ LrNK cells exhibited robust polyfunctional cytokine responses and reduced expression of the cytotoxic marker CD107a upon mitogen stimulation in comparison with CD49a\u2212 LrNK cells regardless of infection status. These findings reveal distinct metabolic and functional specialization of hepatic NK cell subsets, underscoring the unique phenotype and functions of CD49a+ LrNK cells in RM, which may offer novel insights and therapeutic opportunities for treating liver inflammation in HIV infection and other chronic liver diseases.<\/jats:p>","DOI":"10.1111\/imcb.70135","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:10:17Z","timestamp":1779927017000},"page":"656-666","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>CD49a<\/scp>\n                    expression defines a metabolically robust, cytokine\u2010biased liver\n                    <scp>NK<\/scp>\n                    cell subset in rhesus macaques during lentivirus infection"],"prefix":"10.1111","volume":"104","author":[{"given":"Andrew","family":"Hudson","sequence":"first","affiliation":[{"name":"Division of Innate and Comparative Immunology, Center for Human Systems Immunology Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa Xin Yu","family":"Wong","sequence":"additional","affiliation":[{"name":"Duke\u2010NUS Medical School  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Verdolin","sequence":"additional","affiliation":[{"name":"Division of Innate and Comparative Immunology, Center for Human Systems Immunology Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Keith","family":"Reeves","sequence":"additional","affiliation":[{"name":"Division of Innate and Comparative Immunology, Center for Human Systems Immunology Duke University School of Medicine  Durham North Carolina USA"},{"name":"Department of Surgery Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordelia","family":"Manickam","sequence":"additional","affiliation":[{"name":"Division of Innate and Comparative Immunology, Center for Human Systems Immunology Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00946"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402756"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02692"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11632-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01676"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ai.2019.11.002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27254"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07665"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1953"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132629"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3065"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/08892220152644160"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/318501"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17849"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.118000"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0201170"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02796"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-3712"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13171464"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501783"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1477776"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401558"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/s90100386"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2017.72"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2016580118"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.190"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-019-0199-z"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2016.3"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-025-10778-7"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00561-z"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00032"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2005.02147.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.772332"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.994498"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01126-10"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.624324"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25715-z"},{"key":"e_1_2_9_39_1","doi-asserted-by":"crossref","DOI":"10.1097\/IN9.0000000000000020","article-title":"Metabolic regulation of NK cell function: implications for immunotherapy","volume":"5","author":"Sohn H","year":"2023","journal-title":"Immunometabolism (Cobham)"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20172168"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.173099"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-180516"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00202"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2022.12724"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adz1565"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aat8116"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601424"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-18-0757"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e22680"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-24-0124"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-44789-z"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107855"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.052"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aba6232"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37181-w"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba4177"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37419-7"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01519-22"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3227"},{"key":"e_1_2_9_60_1","doi-asserted-by":"crossref","unstructured":"McInnesLH MelvilleJ.UMAP: uniform manifold approximation and projection for dimension reduction.2018.","DOI":"10.32614\/CRAN.package.uwot"}],"container-title":["Immunology &amp; Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imcb.70135","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imcb.70135","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imcb.70135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:33:37Z","timestamp":1785854017000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imcb.70135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":59,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/imcb.70135"],"URL":"https:\/\/doi.org\/10.1111\/imcb.70135","archive":["Portico"],"relation":{},"ISSN":["0818-9641","1440-1711"],"issn-type":[{"value":"0818-9641","type":"print"},{"value":"1440-1711","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]},"assertion":[{"value":"2026-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}