{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:42:50Z","timestamp":1786977770462,"version":"build-2736575974"},"reference-count":70,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T00:00:00Z","timestamp":1571961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003407","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":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Celiac disease (CD) is characterized by a spectrum of intestinal inflammatory lesions. Most patients have villous atrophy (overt\u2010CD), while others have a morphologically normal mucosa, despite the presence of CD\u2010specific autoantibodies (potential\u2010CD). As the mechanism responsible for villous atrophy is not completely elucidated, we investigated biomarkers specific for the different celiac lesions. Phenotype and cytokine production of intestinal mucosa cells were analyzed by flow cytometry in gut biopsies of children with overt\u2010 or potential\u2010CD and in healthy controls. Density of TCR\u03b3\u03b4\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells was found markedly enhanced in intestinal mucosa of children with overt\u2010CD compared to potential\u2010CD or controls. By contrast, very few IL4\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells infiltrated the mucosa with villous atrophy compared to morphologically normal mucosa. IL4\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells were classical CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010helper cells (CD161\n                    <jats:sup>\u2212<\/jats:sup>\n                    ), producing or not IFN\u2010\u03b3, and negative for IL17A. Our study demonstrated that the transition to villous atrophy in CD patients is characterized by increased density of TCR\u03b3\u03b4\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells, and concomitant disappearance of IL4\n                    <jats:sup>+<\/jats:sup>\n                    cells. These findings suggest that immunomodulatory mechanisms are active in potential\u2010CD to counteract the inflammatory cascade responsible of villous atrophy. Further studies are required to validate the use of IL4\n                    <jats:sup>+<\/jats:sup>\n                    and TCR\u03b3\u03b4\n                    <jats:sup>+<\/jats:sup>\n                    T\u00a0cells as biomarkers of the different CD forms.\n                  <\/jats:p>","DOI":"10.1002\/eji.201948098","type":"journal-article","created":{"date-parts":[[2019,9,25]],"date-time":"2019-09-25T18:19:08Z","timestamp":1569435548000},"page":"2222-2234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The intestinal expansion of TCR\u03b3\u03b4\n                    <sup>+<\/sup>\n                    and disappearance of IL4\n                    <sup>+<\/sup>\n                    T\u00a0cells suggest their involvement in the evolution from potential to overt celiac disease"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3310-1054","authenticated-orcid":false,"given":"Serena","family":"Vitale","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Cell Biology National Research Council  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Santarlasci","sequence":"additional","affiliation":[{"name":"Denothe Center University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Camarca","sequence":"additional","affiliation":[{"name":"Institute of Food Sciences\u2010CNR  Avellino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Picascia","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology National Research Council  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela Di","family":"Pasquale","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology National Research Council  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariantonia","family":"Maglio","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine &amp; European Laboratory for the Investigation of Food\u2010Induced Diseases University Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Maggi","sequence":"additional","affiliation":[{"name":"Immunology Department Pediatric Hospital Bambino Ges\u00f9, IRCCS  Rome"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8150-8177","authenticated-orcid":false,"given":"Lorenzo","family":"Cosmi","sequence":"additional","affiliation":[{"name":"Denothe Center University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Annunziato","sequence":"additional","affiliation":[{"name":"Denothe Center University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Troncone","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology National Research Council  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Auricchio","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine &amp; European Laboratory for the Investigation of Food\u2010Induced Diseases University Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Gianfrani","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology National Research Council  Naples Italy"},{"name":"Department of Translational Medicine &amp; European Laboratory for the Investigation of Food\u2010Induced Diseases University Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/138955708783498113"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e31821a23d0"},{"key":"e_1_2_7_4_1","first-page":"1424","article-title":"The PreventCD study design: towards new strategies for the prevention of coeliac disease","volume":"22","author":"Hogen Esch C. E.","year":"2010","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0001-2815.2004.00237.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/187153012800493549"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803181"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.07.013"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2005.02.017"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.01.008"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017039"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042737-199910000-00019"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.05.013"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021281"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.12720"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.303"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.390"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70173-9"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40348-016-0048-4"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1991.tb05690.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00948.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1385\/IR:21:2-3:123"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-012-0316-x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30989"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2008.02213.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70134-9"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2013.19"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.36"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.129882"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni0407-345"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2014.06.004"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916930802350789"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.465"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.26"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2011.04510.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.39.6.818"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.030551"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.9.2287"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2002.01798.x"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-005-2480-5"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201500126"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901919"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070663"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxw006"},{"key":"e_1_2_7_45_1","first-page":"155","article-title":"Regulation of CD3, CD4 and CD8 expressions on PMA\u2010activated human peripheral T\u00a0cells","volume":"33","author":"Mao J. H.","year":"2004","journal-title":"Zhejiang Da Xue Xue Bao Yi Xue Ban."},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.8.2.303-313.2001"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01213"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-010-1710-0"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12075"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.10.012"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000001060"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0170270"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu7125515"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2003.07456.x"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.21.11774"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1311861110"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076008"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.039"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(91)90120-I"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00703.x"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005512513007"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.05.004"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12399"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1159\/000260087"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545907"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14452"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12036"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.03.016"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.65.8.909"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu9101050"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646632"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201948098","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.201948098","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201948098","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T21:55:18Z","timestamp":1694210118000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201948098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,25]]},"references-count":70,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1002\/eji.201948098"],"URL":"https:\/\/doi.org\/10.1002\/eji.201948098","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/EJI.201948098\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948098\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948098\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948098\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948098\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948098\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948098\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948098\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201948098\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,25]]},"assertion":[{"value":"2019-01-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}