{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T19:45:49Z","timestamp":1773085549986,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,7,30]],"date-time":"2012-07-30T00:00:00Z","timestamp":1343606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u03b2 reportedly functions as an amplifier of the <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u03b3\u2010mediated activation signal using a reconstitution system. However, the amplification mechanisms in human mast cells (<jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>s) are poorly understood. We previously reported the hyperexpression of <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u03b2 of <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>s in giant papillae from vernal keratoconjunctivitis patients, compared with that in conjunctivae from nonallergic conjunctivitis patients. Elucidation of the molecular mechanisms of the amplification induced by <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u03b2 should provide new targets for novel therapeutic interventions. The aim is to understand in greater details the function of <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u03b2 in human <jats:styled-content style=\"fixed-case\">MC F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content> expression and signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u03b2 and <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>yn expression was reduced using a lentiviral sh<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> silencing technique. Localization of <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>yn and <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u03b2 in cultured <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>s was examined by confocal microscopic analysis. Mediators were measured by <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The diminution of <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u03b2 significantly downregulated cell surface <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content> expression and <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u2010mediated mediator release\/production. The downregulation of <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u2010mediated degranulation was not only due to the decrease in <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content> expression. The diminution of <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u03b2 inhibited the redistribution of <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>yn within the cell membrane following <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>g<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content> sensitization. The diminution of <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>yn in <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>s significantly downregulated <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u2010mediated degranulation. The recombinant cell\u2010penetrating forms of phosphorylated <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u03b2 immunoreceptor tyrosine\u2010based activation motif (<jats:styled-content style=\"fixed-case\">ITAM<\/jats:styled-content>) for intracellular delivery disturbed the interaction between <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>yn and phosphorylated endogenous <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u03b2 <jats:styled-content style=\"fixed-case\">ITAM<\/jats:styled-content>, resulted in inhibiting <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>g<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>\u2010dependent histamine release from <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content>s <jats:italic>in vitro<\/jats:italic> and from giant papillae specimens <jats:italic>ex vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The interaction between <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>yn and <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u03b2 is indispensable for <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b5<jats:styled-content style=\"fixed-case\">RI<\/jats:styled-content>\u2010mediated human <jats:styled-content style=\"fixed-case\">MC<\/jats:styled-content> activation, and specific inhibition of the interaction may represent a new therapeutic strategy for the treatment of human allergic diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1398-9995.2012.02879.x.","type":"journal-article","created":{"date-parts":[[2012,7,30]],"date-time":"2012-07-30T07:17:22Z","timestamp":1343632642000},"page":"1241-1249","source":"Crossref","is-referenced-by-count":15,"title":["The interaction between <scp>L<\/scp>yn and <scp>F<\/scp>c\u03b5<scp>RI<\/scp>\u03b2 is indispensable for <scp>F<\/scp>c\u03b5<scp>RI<\/scp>\u2010mediated human mast cell activation"],"prefix":"10.1111","volume":"67","author":[{"given":"Y.","family":"Okayama","sequence":"first","affiliation":[{"name":"Division of Molecular Cell Immunology and Allergology Department of Biomedical Sciences Nihon University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.\u2010I.","family":"Kashiwakura","sequence":"additional","affiliation":[{"name":"Division of Molecular Cell Immunology and Allergology Department of Biomedical Sciences Nihon University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Juntendo University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Sasaki\u2010Sakamoto","sequence":"additional","affiliation":[{"name":"Division of Molecular Cell Immunology and Allergology Department of Biomedical Sciences Nihon University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Nunomura","sequence":"additional","affiliation":[{"name":"Division of Molecular Cell Immunology and Allergology Department of Biomedical Sciences Nihon University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Kyoto Prefectural University of Medicine Kyoto 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