{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T01:48:54Z","timestamp":1781920134444,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,4,15]],"date-time":"2018-04-15T00:00:00Z","timestamp":1523750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Epicutaneous sensitization to food allergens can occur through defective skin barriers. However, the relationship between oral tolerance and epicutaneous sensitization remains to be elucidated. We aimed to determine whether prior oral exposure to whey proteins or their hydrolysates prevents epicutaneous sensitization and subsequent food\u2010allergic reaction to the whey protein, \u03b2\u2010lactoglobulin (\u03b2\u2010<jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content>), and investigated the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/c mice were given whey protein concentrate (<jats:styled-content style=\"fixed-case\">WPC<\/jats:styled-content>), two kinds of partial whey protein hydrolysate (<jats:styled-content style=\"fixed-case\">PWH<\/jats:styled-content>1 or <jats:styled-content style=\"fixed-case\">PWH<\/jats:styled-content>2), or extensive whey protein hydrolysate (<jats:styled-content style=\"fixed-case\">EWH<\/jats:styled-content>) in drinking water for 21\u00a0days. The mice were then epicutaneously sensitized with \u03b2\u2010<jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content> on tape\u2010stripped skin. Sensitization was assessed by basophil activation tests and by measuring the level of serum \u03b2\u2010<jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content>\u2010specific antibodies and cytokines secreted from \u03b2\u2010<jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content>\u2010restimulated spleen and mesenteric lymph node (<jats:styled-content style=\"fixed-case\">MLN<\/jats:styled-content>) cells. Development of an allergic reaction was assessed by monitoring body temperature and by measuring mast cell protease\u20101 level in plasma after the \u03b2\u2010<jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content> oral challenge. Activated T\u2010cell population among \u03b2\u2010<jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content>\u2010restimulated <jats:styled-content style=\"fixed-case\">MLN<\/jats:styled-content> cells was also analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In mice fed with <jats:styled-content style=\"fixed-case\">WPC<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> PWH<\/jats:styled-content>1, or <jats:styled-content style=\"fixed-case\">PWH<\/jats:styled-content>2, sensitization and the development of an allergic reaction were totally reduced. The acceleration of cytokine release from the spleen and <jats:styled-content style=\"fixed-case\">MLN<\/jats:styled-content> cells or T\u2010cell activation was not evident after \u03b2\u2010<jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content> restimulation. In <jats:styled-content style=\"fixed-case\">EWH<\/jats:styled-content>\u2010fed mice, a suppressive effect, though milder than that in <jats:styled-content style=\"fixed-case\">WPC<\/jats:styled-content>\u2010, <jats:styled-content style=\"fixed-case\">PWH<\/jats:styled-content>1\u2010, or <jats:styled-content style=\"fixed-case\">PWH<\/jats:styled-content>2\u2010fed mice, was observed during the development of the allergic reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Prior oral exposure to partially hydrolyzed whey protein prevents epicutaneous sensitization and subsequent allergic response to \u03b2\u2010<jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content> in mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pai.12887","type":"journal-article","created":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T17:30:48Z","timestamp":1520530248000},"page":"433-440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Ingestion of partially hydrolyzed whey protein suppresses epicutaneous sensitization to \u03b2\u2010lactoglobulin in mice"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7407-2451","authenticated-orcid":false,"given":"Takeshi","family":"Matsubara","sequence":"first","affiliation":[{"name":"Wellness &amp; Nutrition Science Institute Morinaga Milk Industry Co., Ltd.  Zama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Wellness &amp; Nutrition Science Institute Morinaga Milk Industry Co., Ltd.  Zama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Nakazato","sequence":"additional","affiliation":[{"name":"Wellness &amp; Nutrition Science Institute Morinaga Milk Industry Co., Ltd.  Zama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Wellness &amp; Nutrition Science Institute Morinaga Milk Industry Co., Ltd.  Zama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Ehara","sequence":"additional","affiliation":[{"name":"Wellness &amp; Nutrition Science Institute Morinaga Milk Industry Co., Ltd.  Zama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohisa","family":"Izumi","sequence":"additional","affiliation":[{"name":"Wellness &amp; Nutrition Science Institute Morinaga Milk Industry Co., Ltd.  Zama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Takeda","sequence":"additional","affiliation":[{"name":"Wellness &amp; Nutrition Science Institute Morinaga Milk Industry Co., Ltd.  Zama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1939-4551-6-21"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.02.037"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)60863-X"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aller.2010.05.005"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.10.049"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.11.032"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.01.021"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.156.11.4079"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxu058"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12960"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3038.2011.01205.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000363110"},{"key":"e_1_2_7_14_1","first-page":"673","article-title":"A specific mixture of fructo\u2010oligosaccharides and bifidobacterium breve M\u201016V facilitates partial non\u2010responsiveness to whey protein in mice orally exposed to beta\u2010lactoglobulin\u2010derived peptides","volume":"7","author":"Kostadinova AI","year":"2016","journal-title":"Front Immunol"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2011.02653.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.S0022-0302(90)78910-2"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2015.11.024"},{"key":"e_1_2_7_18_1","first-page":"47","article-title":"IL\u201021R is essential for epicutaneous sensitization and allergic skin inflammation in humans and mice","volume":"119","author":"Jin H","year":"2009","journal-title":"J Clin Invest"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.67"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2008.03154.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.239"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(97)70235-5"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.02.035"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.12120"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.07.033"},{"key":"e_1_2_7_26_1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.4049\/jimmunol.149.2.521","article-title":"Transforming growth factor\u2010beta 1 inhibits murine immediate and delayed type hypersensitivity","volume":"149","author":"Meade R","year":"1992","journal-title":"J Immunol"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/376177a0"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2005.00280.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.5.3287"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2006.01012.x"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.11.009"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.01.063"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.08.041"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1159\/000053832"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3038.2009.00924.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.02.036"}],"container-title":["Pediatric Allergy and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpai.12887","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pai.12887","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T23:55:33Z","timestamp":1695513333000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pai.12887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,15]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/pai.12887"],"URL":"https:\/\/doi.org\/10.1111\/pai.12887","archive":["Portico"],"relation":{},"ISSN":["0905-6157","1399-3038"],"issn-type":[{"value":"0905-6157","type":"print"},{"value":"1399-3038","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,15]]},"assertion":[{"value":"2018-02-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}