{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T19:40:05Z","timestamp":1787859605018,"version":"build-2784847793"},"reference-count":28,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,7]],"date-time":"2020-03-07T00:00:00Z","timestamp":1583539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K16586"],"award-info":[{"award-number":["19K16586"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cross-linking of antigen-specific IgE bound to the high-affinity IgE receptor (Fc\u03b5RI) on the surface of mast cells with multivalent antigens results in the release of mediators and development of type 2 inflammation. Fc\u03b5RI expression and IgE synthesis are, therefore, critical for type 2 inflammatory disease development. In an attempt to clarify the relationship between eosinophilic chronic rhinosinusitis (ECRS) and mast cell infiltration, we analyzed mast cell infiltration at lesion sites and determined its clinical significance. Mast cells are positive for c-kit, and IgE in uncinated tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. The number of positive cells and clinicopathological factors were analyzed. Patients with ECRS exhibited high levels of total IgE serum levels and elevated peripheral blood eosinophil ratios. As a result, the number of mast cells with membranes positive for c-kit and IgE increased significantly in lesions forming NP. Therefore, we classified IgE-positive mast cells into two groups: membrane IgE-positive cells and cytoplasmic IgE-positive cells. The amount of membrane IgE-positive mast cells was significantly increased in moderate ECRS. A positive correlation was found between the membrane IgE-positive cells and the radiological severity score, the ratio of eosinophils, and the total serum IgE level. The number of cytoplasmic IgE-positive mast cells was significantly increased in moderate and severe ECRS. A positive correlation was observed between the cytoplasmic IgE-positive cells and the radiological severity score, the ratio of eosinophils in the blood, and the total IgE level. These results suggest that the process of mast cell internalization of antigens via the IgE receptor is involved in ECRS pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms21051843","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T05:37:34Z","timestamp":1583732254000},"page":"1843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Clinical Significance of Cytoplasmic IgE-Positive Mast Cells in Eosinophilic Chronic Rhinosinusitis"],"prefix":"10.3390","volume":"21","author":[{"given":"Yuka","family":"Gion","sequence":"first","affiliation":[{"name":"Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama 700-8558, Japan"},{"name":"Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Okano","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology of Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan."},{"name":"Department of Otorhinolaryngology, International University of Health and Welfare Graduate School of Medicine, Narita 286-8686, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Koyama","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology of Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tokie","family":"Oura","sequence":"additional","affiliation":[{"name":"Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asami","family":"Nishikori","sequence":"additional","affiliation":[{"name":"Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yorihisa","family":"Orita","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, Kumamoto University Graduate School, Kumamoto 860-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2909-4069","authenticated-orcid":false,"given":"Tomoyasu","family":"Tachibana","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Japanese Red Cross Society Himeji Hospital, Himeji 670-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Marunaka","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology of Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8727-9846","authenticated-orcid":false,"given":"Takuma","family":"Makino","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology of Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Nishizaki","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology of Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5234-6861","authenticated-orcid":false,"given":"Yasuharu","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama 700-8558, Japan"},{"name":"Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1159\/000126066","article-title":"Chronic rhinosinusitis: Risk factors for the recurrence of chronic rhinosinusitis based on 5-year follow-up after endoscopic sinus surgery","volume":"146","author":"Matsuwaki","year":"2008","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.alit.2019.07.002","article-title":"Eosinophilic chronic rhinosinusitis","volume":"68","author":"Fujieda","year":"2019","journal-title":"Allergol. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2332\/allergolint.10-RAI-0231","article-title":"Eosinophilic chronic rhinosinusitis in Japan","volume":"59","author":"Ishitoya","year":"2010","journal-title":"Allergol. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"247","DOI":"10.2332\/allergolint.10-RAI-0202","article-title":"Pathological mechanisms and clinical features of eosinophilic chronic rhinosinusitis in the Japanese population","volume":"59","author":"Takeno","year":"2010","journal-title":"Allergol. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1111\/all.12644","article-title":"Novel scoring system and algorithm for classifying chronic rhinosinusitis: The JESREC study","volume":"70","author":"Tokunaga","year":"2015","journal-title":"Allergy"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1040-8428(99)00010-4","article-title":"Immunopathology and human mast cell cytokines","volume":"31","author":"Bradding","year":"1999","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1034\/j.1600-0625.2001.100101.x","article-title":"Mast cells as initiators of immunity and host defense","volume":"10","author":"Henz","year":"2001","journal-title":"Exp. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1152\/physrev.1997.77.4.1033","article-title":"Mast cells","volume":"77","author":"Metcalfe","year":"1997","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/ni1158","article-title":"Mast cells in the development of adaptive immune responses","volume":"6","author":"Galli","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/nature05010","article-title":"Mast cells are essential intermediaries in regulatory T-cell tolerance","volume":"442","author":"Lu","year":"2006","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.4049\/jimmunol.167.4.2250","article-title":"Protective roles of mast cells against enterobacterial infection are mediated by Toll-like receptor 4","volume":"167","author":"Supajatura","year":"2001","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1172\/JCI0214704","article-title":"Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity","volume":"109","author":"Supajatura","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1172\/JCI119311","article-title":"Nasal mast cells in perennial allergic rhinitics exhibit increased expression of the Fc epsilonRI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells","volume":"99","author":"Pawankar","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.molimm.2008.09.002","article-title":"Endosomal trafficking of the ligated FcvarepsilonRI receptor","volume":"46","author":"Fattakhova","year":"2009","journal-title":"Mol. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4464","DOI":"10.1073\/pnas.83.12.4464","article-title":"Two types of human mast cells that have distinct neutral protease compositions","volume":"83","author":"Irani","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.anai.2017.05.019","article-title":"Distribution, subtype population, and IgE positivity of mast cells in chronic rhinosinusitis with nasal polyps","volume":"119","author":"Baba","year":"2017","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4656","DOI":"10.1038\/s41598-018-23043-9","article-title":"Mast cells exhibiting strong cytoplasmic staining for IgE and high affinity IgE receptor are increased in IgG4-related disease","volume":"8","author":"Nishida","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.jaci.2010.07.007","article-title":"Presence of IL-5 protein and IgE antibodies to staphylococcal enterotoxins in nasal polyps is associated with comorbid asthma","volume":"126","author":"Bachert","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jaci.2007.08.059","article-title":"Staphylococcus aureus enterotoxin B, protein A, and lipoteichoic acid stimulations in nasal polyps","volume":"121","author":"Patou","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jaci.2007.09.036","article-title":"Anti-IgE (omalizumab): A new therapeutic approach for chronic rhinosinusitis","volume":"121","author":"Grundmann","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_21","first-page":"448","article-title":"Omalizumab: A potential new therapeutic approach for aspirin-exacerbated respiratory disease","volume":"20","author":"Bobolea","year":"2010","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.alit.2015.01.004","article-title":"Association and management of eosinophilic inflammation in upper and lower airways","volume":"64","author":"Okano","year":"2015","journal-title":"Allergol. Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jaci.2011.07.056","article-title":"Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis","volume":"128","author":"Gevaert","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Koyama, T., Kariya, S., Sato, Y., Gion, Y., Higaki, T., Haruna, T., Fujiwara, T., Minoura, A., Takao, S., and Orita, Y. (2018). Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis. Allergol. Int.","DOI":"10.1016\/j.alit.2018.09.002"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1002\/lary.25798","article-title":"Eosinophilic esophagitis strongly linked to chronic rhinosinusitis","volume":"126","author":"Padia","year":"2016","journal-title":"Laryngoscope"},{"key":"ref_26","first-page":"108","article-title":"International consensus statement on allergy and rhinology: Allergic rhinitis","volume":"8","author":"Wise","year":"2018","journal-title":"Int. Forum. Allergy Rhinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.jaci.2014.07.021","article-title":"Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis","volume":"134","author":"Alexander","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"181402","DOI":"10.1155\/2012\/181402","article-title":"Eosinophilic esophagitis for the otolaryngologist","volume":"2012","author":"Karkos","year":"2012","journal-title":"Int. J. 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