{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:40:11Z","timestamp":1790847611911,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T00:00:00Z","timestamp":1722038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301966"],"award-info":[{"award-number":["82301966"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170892"],"award-info":[{"award-number":["32170892"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2023\u2010JC\u2010YB\u2010638"],"award-info":[{"award-number":["2023\u2010JC\u2010YB\u2010638"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2017MJ8148"],"award-info":[{"award-number":["2017MJ8148"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The migration is the key step for thymic T cells to enter circulation and then lymph nodes (LNs), essential for future immune surveillance. Although promoter\u2010based transcriptional regulation through <jats:italic>Foxo1<\/jats:italic>, <jats:italic>Klf2<\/jats:italic>, <jats:italic>Ccr7<\/jats:italic>, and <jats:italic>Sell<\/jats:italic> regulates T\u2010cell migration, it remains largely unexplored whether and how enhancers are involved in this process. Here we found that the conditional deletion of <jats:italic>Med1<\/jats:italic>, a component of the mediator complex and a mediator between enhancers and RNA polymerase II, caused a reduction of both CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells in LNs, as well as a decrease of CD8<jats:sup>+<\/jats:sup> T cells in the spleen. Importantly, <jats:italic>Med1<\/jats:italic> deletion hindered the migration of thymic \u03b1\u03b2T cells into the circulation and then into LNs, accompanied by the downregulation of KLF2, CCR7, and CD62L. Mechanistically, Med1 promotes <jats:italic>Klf2<\/jats:italic> transcription by facilitating Foxo1 binding to the <jats:italic>Klf2<\/jats:italic> enhancer. Furthermore, forced expression of <jats:italic>Klf2<\/jats:italic> rescued <jats:italic>Ccr7<\/jats:italic> and <jats:italic>Sell<\/jats:italic> expression, as well as \u03b1\u03b2T\u2010cell migration into LNs. Collectively, our study unveils a crucial role for Med1 in regulating the enhancer\u2010based Foxo1\u2010Klf2 transcriptional program and the migration of \u03b1\u03b2T cells into LNs, providing valuable insights into the molecular mechanisms underlying T\u2010cell migration.<\/jats:p>","DOI":"10.1002\/eji.202350887","type":"journal-article","created":{"date-parts":[[2024,7,28]],"date-time":"2024-07-28T05:25:45Z","timestamp":1722144345000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Med1 controls thymic T\u2010cell migration into lymph node through enhancer\u2010based Foxo1\u2010Klf2 transcription program"],"prefix":"10.1002","author":[{"given":"Ning","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Infection and Immunity, Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Infection and Immunity, Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Infection and Immunity, Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi Province China"},{"name":"Department of Kidney Transplantation, Hospital of Nephropathy The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Organ Transplantation Xi'an Jiaotong University  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Infection and Immunity, Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianzhe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Infection and Immunity, Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi Province China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Basic and Translational Research Laboratory of Immune Related Diseases  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Infection and Immunity, Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi Province China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Basic and Translational Research Laboratory of Immune Related Diseases  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Infection and Immunity, Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi Province China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Basic and Translational Research Laboratory of Immune Related Diseases  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Infection and Immunity, Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi Province China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Basic and Translational Research Laboratory of Immune Related Diseases  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjun","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Infection and Immunity, Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi Province China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Basic and Translational Research Laboratory of Immune Related Diseases  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Infection and Immunity, Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi Province China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Basic and Translational Research Laboratory of Immune Related Diseases  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Infection and Immunity, Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi Province China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Basic and Translational Research Laboratory of Immune Related Diseases  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baojun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Institute of Infection and Immunity, Translational Medicine Institute Xi'an Jiaotong University Health Science Center  Xi'an Shaanxi Province China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases Xi'an Jiaotong University  Xi'an Shaanxi Province China"},{"name":"Basic and Translational Research Laboratory of Immune Related Diseases  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2989"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1223"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2974"},{"key":"e_1_2_9_5_1","first-page":"37","article-title":"T cell homing and exercise","volume":"13","author":"Kruger K.","year":"2007","journal-title":"Exerc. Immunol. Rev."},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3442"},{"key":"e_1_2_9_7_1","first-page":"5","article-title":"A cell\u2010surface molecule involved in organ\u2010specific homing of lymphocytes","volume":"177","author":"Gallatin W. M.","year":"2006","journal-title":"J. Immunol."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.090501.080131"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.10.018"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1222"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200010053431407"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02284"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.12.7632"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04882"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139221"},{"key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/cmi.2014.11","article-title":"Do PI3\u2010kinase mutations drive T cells insane?","volume":"11","author":"Vermijlen D.","year":"2014","journal-title":"Mol. Immunol."},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1603"},{"key":"e_1_2_9_18_1","doi-asserted-by":"crossref","DOI":"10.3390\/vaccines9101171","article-title":"Kruppel\u2010like factor 2 (KLF2) in immune cell migration","volume":"9","author":"Wittner J.","year":"2021","journal-title":"Vaccines"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.5.2980"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1689"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2010.10.005"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2011.07.026"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.03.026"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.bcmd.2006.10.133","article-title":"The mediator complex functions as a coactivator for GATA\u20101 in erythropoiesis via subunit Med1\/TRAP220","volume":"38","author":"Borggrefe T.","year":"2007","journal-title":"Blood Cells Mol. Dis."},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2006-0208"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp306"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.05.015"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000121200"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109095108"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16465"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200037"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170271"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401871"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3298"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3646"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.03.010"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5258.60"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.202350887","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,28]],"date-time":"2024-07-28T05:25:52Z","timestamp":1722144352000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.202350887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,27]]},"references-count":36,"alternative-id":["10.1002\/eji.202350887"],"URL":"https:\/\/doi.org\/10.1002\/eji.202350887","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,27]]},"assertion":[{"value":"2023-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2350887"}}