{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:21:36Z","timestamp":1774689696643,"version":"3.50.1"},"reference-count":114,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,7,16]],"date-time":"2014-07-16T00:00:00Z","timestamp":1405468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This viewpoint presents a unifying concept for the treatment of atopic dermatitis (<jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>) that is based on the improvement of deficient Notch signalling, which appears to represent the fundamental epithelial defect of <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> resulting in epidermal and immunological barrier dysfunction. One study of <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> patients demonstrated a marked epidermal deficiency of Notch receptors and several mouse models with genetically suppressed Notch signalling exhibit dry skin, signs of scratching, skin barrier abnormalities, increased transepidermal water loss and Th2 cell\u2010mediated immunological changes closely resembling human <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>. Notch signalling is critically involved in the differentiation of regulatory T cells, in the feedback inhibition of activated innate immunity, in the repression of activating protein\u20101 (<jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\u20101), the regulation of late epidermal differentiation associated with filaggrin\u2010 and stratum corneum barrier lipid processing, in aquaporin 3\u2010 and claudin\u20101 expression and in keratinocyte\u2010mediated release of thymic stromal lymphopoietin (<jats:styled-content style=\"fixed-case\">TSLP<\/jats:styled-content>), which promotes Th2\u2010driven immune responses with <jats:styled-content style=\"fixed-case\">TSLP<\/jats:styled-content>\u2010 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201031\u2010mediated stimulation of cutaneous sensory neurons involved in the induction of itch. Translational evidence will be provided that all major therapeutic regimens employed for the treatment of <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> such as glucocorticoids, calcineurin inhibitors and <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> radiation may converge in the upregulation of impaired Notch signalling, the proposed pathogenic defect of <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/exd.12460","type":"journal-article","created":{"date-parts":[[2014,5,31]],"date-time":"2014-05-31T10:42:04Z","timestamp":1401532924000},"page":"696-700","source":"Crossref","is-referenced-by-count":6,"title":["Does therapeutic intervention in atopic dermatitis normalize epidermal <scp>N<\/scp>otch deficiency?"],"prefix":"10.1111","volume":"23","author":[{"given":"Bodo C.","family":"Melnik","sequence":"first","affiliation":[{"name":"Department of Dermatology, Environmental Medicine and Health Theory University of Osnabr\u00fcck Osnabr\u00fcck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,7,16]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401036"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-0899-4_10"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-0899-4_1"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a017772"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009258"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2011.09.005"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.770"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200811141"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8108"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033414"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006728"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/fly.18823"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00406-09"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.03.045"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.2332\/allergolint.11-RAI-0395"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm910"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.006775"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.055210"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.01.005"},{"key":"e_1_2_14_21_1","first-page":"615","volume":"77","author":"Xing Z","year":"1997","journal-title":"Lab Invest"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00149.x"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00301.2009"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311510200"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051745"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2010.10.020"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1852"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2012.01487.x"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3038.2011.01241.x"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.10.042"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-171942"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.12.1110"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0625.2002.110102.x"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.08.057"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.10.048"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/942375"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.09.002"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-397925-4.00021-3"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2007.03.013"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M607630200"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.323"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1055642"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.310375"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.01.022"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.133"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2013.10.001"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.13.3427"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1477606"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2008.01.017"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015842"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.325"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.272"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112258"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.08.034"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2013.09.011"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1988.tb03262.x"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12470233"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060123"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.507"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.10.018"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-304241"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-007-0027-z"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12058"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2006.01151.x"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.395"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080179"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-1070com"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.07.006"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.5021\/ad.2013.25.4.410"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.09.015"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2011.11.003"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.402"},{"key":"e_1_2_14_73_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1100721"},{"key":"e_1_2_14_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2011.02767.x"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1159\/000350769"},{"key":"e_1_2_14_76_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115747"},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80105-3"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80054-0"},{"key":"e_1_2_14_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80643-3"},{"key":"e_1_2_14_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.02.020"},{"key":"e_1_2_14_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2061"},{"key":"e_1_2_14_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242643"},{"key":"e_1_2_14_83_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.6.2896"},{"key":"e_1_2_14_84_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01295-13"},{"key":"e_1_2_14_85_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2010.03942.x"},{"key":"e_1_2_14_86_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10125"},{"key":"e_1_2_14_87_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2002-0006"},{"key":"e_1_2_14_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204388"},{"key":"e_1_2_14_89_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63103"},{"key":"e_1_2_14_90_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1484707"},{"key":"e_1_2_14_91_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02119-06"},{"key":"e_1_2_14_92_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1406006"},{"key":"e_1_2_14_93_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-013-0013-9"},{"key":"e_1_2_14_94_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.3.5357"},{"key":"e_1_2_14_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2013.03.022"},{"key":"e_1_2_14_96_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.18.7914-7930.2004"},{"key":"e_1_2_14_97_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.5.1737-1749.2003"},{"key":"e_1_2_14_98_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204385"},{"key":"e_1_2_14_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2013.01.005"},{"key":"e_1_2_14_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.02.016"},{"key":"e_1_2_14_101_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.089920"},{"key":"e_1_2_14_102_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0781.2007.00291.x"},{"key":"e_1_2_14_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.45"},{"key":"e_1_2_14_104_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950180210"},{"key":"e_1_2_14_105_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004030100216"},{"key":"e_1_2_14_106_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2001.01441.x"},{"key":"e_1_2_14_107_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12476124"},{"key":"e_1_2_14_108_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2013.1175"},{"key":"e_1_2_14_109_1","first-page":"49","volume":"4","author":"Reichrath S","year":"2012","journal-title":"Dermatoendocrinol"},{"key":"e_1_2_14_110_1","author":"Kim J E","year":"2014","journal-title":"Acta Derm Venereol"},{"key":"e_1_2_14_111_1","first-page":"115","volume":"6","author":"Wiegand C","year":"2013","journal-title":"Clin Cosmet Investig Dermatol"},{"key":"e_1_2_14_112_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2007.02351.x"},{"key":"e_1_2_14_113_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12120"},{"key":"e_1_2_14_114_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-7-49"},{"key":"e_1_2_14_115_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.350678"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fexd.12460","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.12460","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T16:13:53Z","timestamp":1695572033000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.12460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,16]]},"references-count":114,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1111\/exd.12460"],"URL":"https:\/\/doi.org\/10.1111\/exd.12460","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,16]]}}}