{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:46:32Z","timestamp":1791549992825,"version":"4.3.4"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T00:00:00Z","timestamp":1555372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2019.00806","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T01:04:51Z","timestamp":1555376691000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":48,"title":["Intestinal Epithelial Cells-Derived Hypoxia-Inducible Factor-1\u03b1 Is Essential for the Homeostasis of Intestinal Intraepithelial Lymphocytes"],"prefix":"10.3389","volume":"10","author":[{"given":"Lihua","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,4,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/nature10208","article-title":"Intestinal homeostasis and its breakdown in inflammatory bowel disease","volume":"474","author":"Maloy","year":"2011","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nri2316","article-title":"Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut","volume":"8","author":"Artis","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1038\/nature05590","article-title":"Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis","volume":"446","author":"Zaph","year":"2007","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/nature05698","article-title":"Epithelial NEMO links innate immunity to chronic intestinal inflammation","volume":"446","author":"Nenci","year":"2007","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1084\/jem.20062211","article-title":"Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells","volume":"204","author":"Allakhverdi","year":"2007","journal-title":"J Exp Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1111\/j.0105-2896.2005.00290.x","article-title":"Mucosal immunoglobulins","volume":"206","author":"Woof","year":"2005","journal-title":"Immunol Rev"},{"key":"B7","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1097\/SLA.0b013e31818a1522","article-title":"Intestinal specific overexpression of interleukin-7 attenuates the alternation of intestinal intraepithelial lymphocytes after total parenteral nutrition administration","volume":"248","author":"Yang","year":"2008","journal-title":"Ann Surg"},{"key":"B8","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.it.2008.08.003","article-title":"T-cell recruitment to the intestinal mucosa","volume":"29","author":"Agace","year":"2008","journal-title":"Trends Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1084\/jem.20062446","article-title":"Sphingosine 1-phosphate dependence in the regulation of lymphocyte trafficking to the gut epithelium","volume":"204","author":"Kunisawa","year":"2007","journal-title":"J Exp Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1615\/CritRevImmunol.v18.i3.40","article-title":"Intraepithelial lymphocytes: origins, distribution, and function","volume":"18","author":"Beagley","year":"1998","journal-title":"Crit Rev Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.imlet.2010.09.004","article-title":"TL and CD8alphaalpha: enigmatic partners in mucosal immunity","volume":"134","author":"Olivares-Villagomez","year":"2010","journal-title":"Immunol Lett"},{"key":"B12","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.immuni.2014.06.018","article-title":"The transcription factor T-bet is induced by IL-15 and thymic agonist selection and controls CD8alphaalpha(+) intraepithelial lymphocyte development","volume":"41","author":"Klose","year":"2014","journal-title":"Immunity"},{"key":"B13","doi-asserted-by":"publisher","first-page":"4281865","DOI":"10.1155\/2016\/4281865","article-title":"TLR2-dependent signaling for IL-15 production is essential for the homeostasis of intestinal intraepithelial lymphocytes","volume":"2016","author":"Qiu","year":"2016","journal-title":"Mediators Inflamm"},{"key":"B14","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1038\/ni1101-997","article-title":"Intraepithelial lymphocytes: exploring the Third Way in immunology","volume":"2","author":"Hayday","year":"2001","journal-title":"Nat Immunol"},{"key":"B15","doi-asserted-by":"crossref","first-page":"707","DOI":"10.4049\/jimmunol.161.2.707","article-title":"The role of IL-7 in thymic and extrathymic development of TCR gamma delta cells","volume":"161","author":"Laky","year":"1998","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1172\/JCI118002","article-title":"Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes","volume":"95","author":"Watanabe","year":"1995","journal-title":"J Clin Invest"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.4049\/jimmunol.0900420","article-title":"Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8alphaalpha IELs","volume":"183","author":"Ma","year":"2009","journal-title":"J Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1111\/j.1365-2249.2004.02431.x","article-title":"Human intestinal epithelial cell-derived interleukin (IL)-18, along with IL-2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes","volume":"136","author":"Okazawa","year":"2004","journal-title":"Clin Exp Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1016\/j.celrep.2017.04.046","article-title":"Epithelial histone deacetylase 3 instructs intestinal immunity by coordinating local lymphocyte activation","volume":"19","author":"Navabi","year":"2017","journal-title":"Cell Rep"},{"key":"B20","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1146\/annurev.immunol.22.012703.104731","article-title":"Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors","volume":"22","author":"Sitkovsky","year":"2004","journal-title":"Annu Rev Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1084\/jem.20050177","article-title":"HIF-1-dependent repression of equilibrative nucleoside transporter (ENT) in hypoxia","volume":"202","author":"Eltzschig","year":"2005","journal-title":"J Exp Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/ni.1683","article-title":"Hypoxia-inducible factor-dependent induction of netrin-1 dampens inflammation caused by hypoxia","volume":"10","author":"Rosenberger","year":"2009","journal-title":"Nat Immunol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40348-016-0030-1","article-title":"The role of hypoxia in intestinal inflammation","volume":"3","author":"Shah","year":"2016","journal-title":"Mol Cell Pediatr"},{"key":"B24","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.apsb.2015.05.007","article-title":"HIF-1alpha pathway: role, regulation and intervention for cancer therapy","volume":"5","author":"Masoud","year":"2015","journal-title":"Acta Pharm Sin B"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.2174\/138161206777698783","article-title":"Natural product-derived small molecule activators of hypoxia-inducible factor-1 (HIF-1)","volume":"12","author":"Nagle","year":"2006","journal-title":"Curr Pharm Des"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1172\/JCI200421086","article-title":"Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis","volume":"114","author":"Karhausen","year":"2004","journal-title":"J Clin Invest"},{"key":"B27","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1053\/j.gastro.2007.10.012","article-title":"The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis","volume":"134","author":"Cummins","year":"2008","journal-title":"Gastroenterology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/cei.12896","article-title":"Hypoxia inducible factor-1alpha-induced interleukin-33 expression in intestinal epithelia contributes to mucosal homeostasis in inflammatory bowel disease","volume":"187","author":"Sun","year":"2017","journal-title":"Clin Exp Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/mi.2015.67","article-title":"Hypoxia-inducible factor 1 in dendritic cells is crucial for the activation of protective regulatory T cells in murine colitis","volume":"9","author":"Fluck","year":"2016","journal-title":"Mucosal Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"E2784","DOI":"10.1073\/pnas.1202366109","article-title":"Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa","volume":"109","author":"Clambey","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1242\/dmm.019000","article-title":"HIF1alpha deficiency reduces inflammation in a mouse model of proximal colon cancer","volume":"8","author":"Mladenova","year":"2015","journal-title":"Dis Model Mech"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1007\/s10620-015-3632-x","article-title":"Aryl hydrocarbon receptor activation down-regulates IL-7 and reduces inflammation in a mouse model of DSS-induced colitis","volume":"60","author":"Ji","year":"2015","journal-title":"Dig Dis Sci"},{"key":"B33","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1189\/jlb.3RU1014-465R","article-title":"Role of the intestinal cytokine microenvironment in shaping the intraepithelial lymphocyte repertoire","volume":"97","author":"Qiu","year":"2015","journal-title":"J Leukoc Biol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1146\/annurev.immunol.021908.132657","article-title":"Regulatory lymphocytes and intestinal inflammation","volume":"27","author":"Izcue","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1007\/s00204-017-2139-y","article-title":"Activation of intestinal GR-FXR and PPARalpha-UGT signaling exacerbates ibuprofen-induced enteropathy in mice","volume":"92","author":"Lu","year":"2018","journal-title":"Arch Toxicol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e92","DOI":"10.1590\/s1678-9946201759092","article-title":"HIF-1alpha and infectious diseases: a new frontier for the development of new therapies","volume":"59","author":"Santos","year":"2017","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"B37","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/s10735-013-9544-1","article-title":"Disturbance of intraepithelial lymphocytes in a murine model of acute intestinal ischemia\/reperfusion","volume":"45","author":"Qiu","year":"2014","journal-title":"J Mol Histol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.tibs.2008.08.002","article-title":"HIF-1 regulation: not so easy come, easy go","volume":"33","author":"Yee","year":"2008","journal-title":"Trends Biochem Sci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1089\/jir.2013.0044","article-title":"Interferon-gamma-induced intestinal epithelial barrier dysfunction by NF-kappaB\/HIF-1alpha pathway","volume":"34","author":"Yang","year":"2014","journal-title":"J Interferon Cytokine Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1089\/jir.2013.0040","article-title":"DMOG ameliorates IFN-gamma-induced intestinal barrier dysfunction by suppressing PHD2-dependent HIF-1alpha degradation","volume":"34","author":"Wang","year":"2014","journal-title":"J Interferon Cytokine Res"},{"key":"B41","doi-asserted-by":"publisher","first-page":"13447","DOI":"10.3748\/wjg.v21.i48.13447","article-title":"Hypoxia-inducible factor-1 modulates upregulation of mutT homolog-1 in colorectal cancer","volume":"21","author":"Qiu","year":"2015","journal-title":"World J Gastroenterol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1016\/j.cell.2011.07.033","article-title":"Control of T(H)17\/T(reg) balance by hypoxia-inducible factor 1","volume":"146","author":"Dang","year":"2011","journal-title":"Cell"},{"key":"B43","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/S0092-8674(03)00154-5","article-title":"HIF-1alpha is essential for myeloid cell-mediated inflammation","volume":"112","author":"Cramer","year":"2003","journal-title":"Cell"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1002\/eji.201142053","article-title":"Influence of hypoxia-inducible factor 1alpha on dendritic cell differentiation and migration","volume":"42","author":"Kohler","year":"2012","journal-title":"Eur J Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1161\/CIRCRESAHA.117.305109","article-title":"HIF hydroxylase pathways in cardiovascular physiology and medicine","volume":"117","author":"Bishop","year":"2015","journal-title":"Circ Res"},{"key":"B46","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1203\/00006450-200105000-00002","article-title":"Hypoxia-inducible factor 1: control of oxygen homeostasis in health and disease","volume":"49","author":"Semenza","year":"2001","journal-title":"Pediatr Res"},{"key":"B47","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/j.ccell.2017.10.003","article-title":"An HIF-1alpha\/VEGF-A axis in cytotoxic T cells regulates tumor progression","volume":"32","author":"Palazon","year":"2017","journal-title":"Cancer Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1080\/19490976.2016.1156827","article-title":"The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy","volume":"7","author":"Whitfield-Cargile","year":"2016","journal-title":"Gut Microbes"},{"key":"B49","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/mi.2015.89","article-title":"Mechanisms of NLRP3 inflammasome activation and its role in NSAID-induced enteropathy","volume":"9","author":"Higashimori","year":"2016","journal-title":"Mucosal Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"eaao1135","DOI":"10.1126\/sciimmunol.aao1135","article-title":"GPR55 regulates intraepithelial lymphocyte migration dynamics and susceptibility to intestinal damage","volume":"2","author":"Sumida","year":"2017","journal-title":"Sci Immunol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1986","DOI":"10.1097\/MIB.0000000000000804","article-title":"The roles of cathelicidin LL-37 in inflammatory bowel disease","volume":"22","author":"Sun","year":"2016","journal-title":"Inflamm Bowel Dis"},{"key":"B52","doi-asserted-by":"publisher","first-page":"20834","DOI":"10.1073\/pnas.0808700106","article-title":"Failure of T cell homing, reduced CD4\/CD8alphaalpha intraepithelial lymphocytes, and inflammation in the gut of vitamin D receptor KO mice","volume":"105","author":"Yu","year":"2008","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.00806\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T15:44:28Z","timestamp":1694792668000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.00806\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,16]]},"references-count":52,"alternative-id":["10.3389\/fimmu.2019.00806"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2019.00806","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,16]]},"article-number":"806"}}