{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:24:06Z","timestamp":1791343446201,"version":"4.3.1"},"reference-count":17,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,7,8]],"date-time":"2013-07-08T00:00:00Z","timestamp":1373241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA16058"],"award-info":[{"award-number":["CA16058"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA95426"],"award-info":[{"award-number":["CA95426"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA68458"],"award-info":[{"award-number":["CA68458"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA09338"],"award-info":[{"award-number":["CA09338"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA155521"],"award-info":[{"award-number":["CA155521"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2013,10]]},"abstract":"\n Activation of the fibromyalgia syndrome\u2010like tyrosine kinase 3 (\n FLT<\/jats:styled-content>\n 3) by its ligand,\n FLT<\/jats:styled-content>\n 3 ligand (\n FL<\/jats:styled-content>\n ), strongly augments the development of natural killer (\n NK<\/jats:styled-content>\n ) cells from human\n CD<\/jats:styled-content>\n 34\n +<\/jats:sup>\n hematopoietic progenitor cells (\n HPC<\/jats:styled-content>\n s) in the presence of\n IL<\/jats:styled-content>\n \u201015, compared with\n NK<\/jats:styled-content>\n \u2010cell development in the presence of\n IL<\/jats:styled-content>\n \u201015 alone. In this study, we observed that blocking the receptor tyrosine kinase\n A<\/jats:styled-content>\n xl\/\n G<\/jats:styled-content>\n as6 pathway with a soluble Axl\u2010IgG1 Fc fusion protein (\n A<\/jats:styled-content>\n xl\u2010\n F<\/jats:styled-content>\n c) in the presence of\n FL<\/jats:styled-content>\n significantly diminished the absolute number of\n CD<\/jats:styled-content>\n 3\n \u2212<\/jats:sup>\n CD<\/jats:styled-content>\n 56\n +<\/jats:sup>\n NK<\/jats:styled-content>\n cells derived from human\n CD<\/jats:styled-content>\n 34\n +<\/jats:sup>\n HPC<\/jats:styled-content>\n s. Axl\u2010\n F<\/jats:styled-content>\n c reduced the expression levels of the\n IL<\/jats:styled-content>\n \u20102\/15 receptor \u03b2 chain (\n CD<\/jats:styled-content>\n 122) and \u03b3 chain (\n CD<\/jats:styled-content>\n 132) induced by activation of\n FLT<\/jats:styled-content>\n 3 and consequently reduced the frequency of\n NK<\/jats:styled-content>\n precursor cells responding to\n IL<\/jats:styled-content>\n \u201015. Furthermore,\n A<\/jats:styled-content>\n xl\u2010\n F<\/jats:styled-content>\n c diminished\n FL<\/jats:styled-content>\n \u2010induced\n FLT<\/jats:styled-content>\n 3 phosphorylation and impeded the physical interaction between\n A<\/jats:styled-content>\n xl and\n FLT<\/jats:styled-content>\n 3 in\n CD<\/jats:styled-content>\n 34\n +<\/jats:sup>\n HPC<\/jats:styled-content>\n s. Collectively, our data suggest that the\n A<\/jats:styled-content>\n xl\/\n G<\/jats:styled-content>\n as6 pathway contributes to normal human\n NK<\/jats:styled-content>\n \u2010cell development at least in part via its positive regulatory effect on\n FLT<\/jats:styled-content>\n 3 signaling in\n CD<\/jats:styled-content>\n 34\n +<\/jats:sup>\n HPC<\/jats:styled-content>\n s.\n <\/jats:p>","DOI":"10.1002\/eji.201243116","type":"journal-article","created":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T15:29:06Z","timestamp":1369927746000},"page":"2750-2755","source":"Crossref","is-referenced-by-count":33,"title":["A<\/scp>\n xl\/\n G<\/scp>\n as6 pathway positively regulates FLT3 activation in human natural killer cell development"],"prefix":"10.1002","volume":"43","author":[{"given":"Il\u2010Kyoo","family":"Park","sequence":"first","affiliation":[{"name":"The Comprehensive Cancer Center The Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Trotta","sequence":"additional","affiliation":[{"name":"The Comprehensive Cancer Center The Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Yu","sequence":"additional","affiliation":[{"name":"The Comprehensive Cancer Center The Ohio State University Columbus OH USA"},{"name":"Division of Hematology Department of Internal Medicine The James Cancer Hospital and Solove Research Institute The Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Caligiuri","sequence":"additional","affiliation":[{"name":"The Comprehensive Cancer Center The Ohio State University Columbus OH USA"},{"name":"Division of Hematology Department of Internal Medicine The James Cancer Hospital and Solove Research Institute The Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-004-4274-x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1182\/blood.V82.4.1110.1110","article-title":"Human FLT3\/FLK2 gene: cDNA cloning and expression in hematopoietic cells","volume":"82","author":"Rosnet O.","year":"1993","journal-title":"Blood"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90167-1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.11.3489"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1182\/blood.V92.10.3647","article-title":"Flt3 ligand promotes the generation of a distinct CD34(+) human natural killer cell progenitor that responds to interleukin\u201015","volume":"92","author":"Yu H.","year":"1998","journal-title":"Blood"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05529.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2000.027"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90424-7"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.8.4442"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1353"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-157073"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2009.06.002"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/368643a0"},{"issue":"1","key":"e_1_2_7_15_1","first-page":"99","article-title":"The flt3 ligand: a hematopoietic stem cell factor whose activities are distinct from steel factor","volume":"12","author":"Lyman S. D.","year":"1994","journal-title":"Stem Cells"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2006.04.004"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1182\/blood.V87.7.2632.bloodjournal8772632","article-title":"Role of interleukin\u201015 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells","volume":"87","author":"Mrozek E.","year":"1996","journal-title":"Blood"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.126.4.1614"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201243116","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201243116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T12:32:35Z","timestamp":1696595555000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201243116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,8]]},"references-count":17,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["10.1002\/eji.201243116"],"URL":"https:\/\/doi.org\/10.1002\/eji.201243116","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,8]]}}}