{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T08:29:14Z","timestamp":1782980954010,"version":"3.54.5"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T00:00:00Z","timestamp":1568246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G116\/165"],"award-info":[{"award-number":["G116\/165"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0901998"],"award-info":[{"award-number":["G0901998"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF15CC0018346"],"award-info":[{"award-number":["NNF15CC0018346"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Inosine pranobex (IP) is a synthetic immunomodulating compound, indicated for use in the treatment of human papillomavirus\u2010associated warts and subacute sclerosing panencephalitis. Previous studies demonstrate that the immunomodulatory activity of IP is characterized by enhanced lymphocyte proliferation, cytokine production, and NK cell cytotoxicity. The activation of NKG2D signaling on NK cells, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and \u03b3\u03b4 T cells also produces these outcomes. We hypothesized that IP alters cellular immunity through the induction of NKG2D ligand expression on target cells, thereby enhancing immune cell activation through the NKG2D receptor. We tested this hypothesis and show that exposure of target cells to IP leads to increased expression of multiple NKG2D ligands. Using both targeted metabolic interventions and unbiased metabolomic studies, we found that IP causes an increase in intracellular concentration of purine nucleotides and tricarboxylic acid (TCA) cycle intermediates and NKG2D ligand induction. The degree of NKG2D ligand induction was functionally significant, leading to increased NKG2D\u2010dependent target cell immunogenicity. These findings demonstrate that the immunomodulatory properties of IP are due to metabolic activation with NKG2D ligand induction.\n                  <\/jats:p>","DOI":"10.1002\/eji.201847948","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T18:44:05Z","timestamp":1566413045000},"page":"130-137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Inosine pranobex enhances human NK cell cytotoxicity by inducing metabolic activation and NKG2D ligand expression"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7148-7096","authenticated-orcid":false,"given":"Michael T.","family":"McCarthy","sequence":"first","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine University of Oxford  Oxford OX3 7BN UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Lin","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine University of Oxford  Oxford OX3 7BN UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyoshi","family":"Soga","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences Keio University  Tsuruoka Yamagata 997\u20100052 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Adam","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine University of Oxford  Oxford OX3 7BN UK"},{"name":"Target Discovery Institute Nuffield Department of Medicine University of Oxford  Oxford OX3 7FZ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"O'Callaghan","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine University of Oxford  Oxford OX3 7BN UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2006.01041.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(82)92097-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-0138"},{"key":"e_1_2_7_5_1","first-page":"91","article-title":"Isoprinosine potentiation of human peripheral blood mononuclear cell response to mitogens: kinetics and effect on expression of the IL\u20102 receptor and the activity of interleukin 2","volume":"27","author":"Lomnitzer R.","year":"1988","journal-title":"J Clin Lab Immunol"},{"key":"e_1_2_7_6_1","first-page":"67","article-title":"Immunomodulation by isoprinosine: effects on in vitro immune functions of lymphocytes from humans with autoimmune diseases","volume":"52","author":"Nakamura T.","year":"1983","journal-title":"Clin. Exp. Immunol"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/08923978909005391"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0192-0561(82)90043-1"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0192-0561(86)90074-3"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1990.tb03206.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5428.727"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/85321"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03884"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.282152"},{"key":"e_1_2_7_15_1","first-page":"687","article-title":"MICA Expression Is Regulated by Cell Adhesion and Contact in a FAK\/Src\u2010Dependent Manner","volume":"7","author":"Moncayo G.","year":"2016","journal-title":"Front. Immun."},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-052720"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.809459"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201797138"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-67199-4_568"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00095-4"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324705"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012635"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr034020m"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac900675k"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.09.006"},{"key":"e_1_2_7_26_1","unstructured":"Team R. C. R: A language and environment for statistical computing.R Foundation for Statistical Computing Vienna Austria;2016."}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201847948","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201847948","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.201847948","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201847948","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T10:48:24Z","timestamp":1693997304000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201847948"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,12]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1002\/eji.201847948"],"URL":"https:\/\/doi.org\/10.1002\/eji.201847948","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/EJI.201847948\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847948\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847948\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847948\/v2\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847948\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847948\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847948\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847948\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847948\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847948\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847948\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847948\/v1\/review3","asserted-by":"object"}]},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,12]]},"assertion":[{"value":"2018-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}