Degranulation from mast cell in the onset of allergic rhinitis

• Project/Area Number: 26293368
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: University of Fukui
• Principal Investigator: Fujieda Shigeharu 福井大学, 学術研究院医学系部門, 教授 (30238539)
• Co-Investigator(Kenkyū-buntansha): 徳永 貴広 福井大学, 医学部附属病院, 特命助教 (10464075) ; 野口 恵美子 筑波大学, 医学医療系, 教授 (40344882) ; 高林 哲司 福井大学, 医学部附属病院, 講師 (70397272)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2014: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: スギ花粉症 / HLA-DR / Apolipoprotein A4 / Dectin-1 / TSLP / IL-33 / C3a / C5a / HLA-DPB / Apolipoprotein A-IV / ヒスタミン / CpG-DNA / Hexaponda / アレルギー / 遺伝子 / 細胞・組織 / 発現制御 / 免疫学 / IgE / IL-17A / アレルギー性鼻炎 / Dectin 1 / ヒスタミン遊離

Outline of Final Research Achievements

HLA-DPB1*02:01 and HLA-DPB1*02:02 had a protective tendency and DPB1*05:01 had a susceptible tendency for sensitization of Japanese cedar pollen. Apo A4, which is induced by sublingual immunotherapy, inhibited sneezing, nasal itching and nasal obstruction. Dectin-1 is a critical factor in the tyrosine phosphorylation in mast cells. TSLP and IL-33 are important factors in production of IgE, but not release histamine from mast cells. Serum levels of C3a, C5a and IL-A were associated with symptom scores and increased by sublingual immunotherapy.

Research Products

• [Journal Article] Association of Japanese cedar pollinosis and sensitization with <i>HLA-DPB1</i> in the Japanese adolescent (2018)
  • Author(s): Morii W, Sakai A, Ninomiya T, Kidoguchi M, Sumazaki R, Fujieda S, Noguchi E
  • Journal Title: Allergol. Int. Volume: in press Issue: 1 Pages: 61-66
  • DOI: 10.1016/j.alit.2017.04.004
  • NAID: 130006322040
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Japanese guidelines for allergic rhinitis 2017 (2017)
  • Author(s): Okubo K, Kurono Y, Ichimura K, Enomoto T, Okamoto Y, Kawauchi H, Suzaki H, Fujieda S, Masuyama K
  • Journal Title: Allergol. Int. Volume: 66(2) Issue: 2 Pages: 205-219
  • DOI: 10.1016/j.alit.2016.11.001
  • NAID: 130005628190
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] Complementary and alternative medicine for allergic rhinitis in Japan (2017)
  • Author(s): Yonekura S, Okamoto Y, Sakurai D, Sakurai T, Iinuma T, Yamamoto H, Hanazawa T, Horiguchi S, Kurono Y, Honda K, Majima Y, Masuyama K, Takeda N, Fujieda S, Okano M, Ogino S, Okubo.
  • Journal Title: Allergol. Int. Volume: in press Issue: 3 Pages: 425-431
  • DOI: 10.1016/j.alit.2016.10.006
  • NAID: 130005858792
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] Toll-like receptor ligands induce cytokine and chemokine production in human inner ear endolymphatic sac fibroblasts. (2017)
  • Author(s): Yamada T, Ogi K, Sakashita M, Kanno M, Kubo S, Ito Y, Imoto Y, Tokunaga T, Okamoto M, Narita N, Fujieda S.
  • Journal Title: Auris Nasus Larynx. Volume: 44（4） Pages: 398-403
  • DOI: 10.1016/j.anl.2016.10.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] House dust mite sublingual tablet is effective and safe in patients with allergic rhinitis. (2017)
  • Author(s): Okamoto Y, Fujieda S, Okano M, Yoshida Y, Kakudo S, Masuyama K.
  • Journal Title: Allergy Volume: 72 Pages: 435-443
  • DOI: 10.1111/all.12996
  • Peer Reviewed / Open Access
• [Journal Article] Guiding principles of sublingual immunotherapy for allergic rhinitis in Japanese patients. (2016)
  • Author(s): Masuyama K, Goto M, Takeno S, Ohta N, Okano M, Kamijo A, Suzuki M, Terada T, Sakurai D, Horiguchi S, Honda K, Matsune S, Yamada T, Sakashita M, Yuta A, Fuchiwaki T, Miyanohara I, Nakayama T, Okamoto Y, Fujieda S.
  • Journal Title: Auris Nasus Larynx Volume: 43(1) Pages: 1-9
  • DOI: 10.1016/j.anl.2015.08.015
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Murine allergic rhinitis and nasal Th2 activation are mediated via TSLP- and IL-33-signaling pathways. (2016)
  • Author(s): Akasaki S, Matsushita K, Kato Y, Fukuoka A, Iwasaki N, Nakahira M, Fujieda S, Yasuda K, Yoshimoto T.
  • Journal Title: Int Immunol. Volume: 28 Pages: 65-7
  • DOI: 10.1093/intimm/dxv055
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Nitrite/Nitrate in Nasal Lavage Fluid Reflects Nasal Symptoms After a Single Nasal Allergen Provocation in Patients With Seasonal Allergic Rhinitis. (2015)
  • Author(s): Imoto Y, Yamada T, Tsukahara H, Kimura Y, Kato Y, Sakashita M, Fujieda S.
  • Journal Title: J Investig Allergol Clin Immunol. Volume: 25 Pages: 382-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Peripheral basophil reactivity, CD203c expression by Cryj1 stimulation, is useful for diagnosing seasonal allergic rhinitis by Japanese cedar pollen (2015)
  • Author(s): Imoto Y, Takabayashi T, Sakashita M, Tokunaga T, Ninomiya T, Ito Y, Narita N, Yamada T, Fujieda S
  • Journal Title: Immun Inflamm Dis. Volume: 3 Pages: 300-308
  • DOI: 10.1002/iid3.69
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Long-term sublingual immunotherapy for Japanese cedar pollinosis and the levels of IL-17A and complement components 3a and 5a. (2015)
  • Author(s): Sakashita M, Yamada T, Imoto Y, Hirota T, Tamari M, Ito Y, Kubo S, Osawa Y, Takahashi N, Fujieda S.
  • Journal Title: Cytokine Volume: 75 Pages: 181-5
  • DOI: 10.1016/j.cyto.2015.03.019
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Synergistic suppression of Poly(I:C)-induced CCL3 by a corticosteroid and a long acting &beta;2 agonist in nasal epithelial cells (2015)
  • Author(s): Tanaka S, Tamari M, Nakayama T, et al.
  • Journal Title: Allergol. Int. Volume: 64(2) Issue: 2 Pages: 196-199
  • DOI: 10.1016/j.alit.2014.10.006
  • NAID: 130005290257
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association and management of eosinophilic inflammation in upper and lower airways (2015)
  • Author(s): Okano M, Kariya S, Ohta N, et al.
  • Journal Title: Allergol. Int. Volume: 64(2) Issue: 2 Pages: 131-138
  • DOI: 10.1016/j.alit.2015.01.004
  • NAID: 130005290337
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulation of upper airway inflammation facilitates comfortable breathing. (2015)
  • Author(s): Fujieda S, Izuhara K.
  • Journal Title: Allergol Int. Volume: 64(2) Pages: 119-120
  • NAID: 130005290286
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Factors associated with the development and remission of allergic diseases in an epidemiological survey of high school students in Japan. (2015)
  • Author(s): Tokunaga T, Ninomiya T, Osawa Y, Imoto Y, Ito Y, Takabayashi T, Narita N, Kijima A, Murota H, Katayama I, Fujieda S.
  • Journal Title: Am J Rhinol Allergy Volume: 29 Pages: 94-9
  • DOI: 10.2500/ajra.2015.29.4135
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ishii-Mizuno Y, Umeki Y, Takahashi Y, Kato Y, Takabayashi T, Fujieda S, Takakura Y, Nishikawa M. Nasal delivery of Japanese cedar pollen Cryj1 by using self-gelling immunostimulatory DNA for effective induction of immune responses in mice (2015)
  • Author(s): Ishii-Mizuno Y, Umeki Y, Takahashi Y, Kato Y, Takabayashi T, Fujieda S, Takakura Y, Nishikawa M
  • Journal Title: J Control Release Volume: 200 Pages: 52-59
  • DOI: 10.1016/j.jconrel.2014.12.040
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 粘膜アレルギー：花粉症 (2015)
  • Author(s): 藤枝重治、坂下雅文、意元義政、高林哲司、山田武千代
  • Journal Title: 炎症と免疫 Volume: 23（1） Pages: 61-67
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dectin-1-mediated signaling leads to characteristic gene expressions and cytokine secretion via spleen tyrosine kinase (Syk) in rat mast cells. (2014)
  • Author(s): Kimura Y, Chihara K, Honjoh C, Takeuchi K, Yamauchi S, Yoshiki H, Fujieda S, Sada K
  • Journal Title: J. Biol. Chem. Volume: 289 Pages: 31565-31575
  • DOI: 10.1074/jbc.m114.581322
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Nasal sensitization with ragweed pollen induces local-allergic-rhinitis-like symptoms in mice. (2014)
  • Author(s): Kato Y, Akasaki S, Muto-Haenuki Y, Fujieda S, Matsushita K, Yoshimoto T.
  • Journal Title: PLoS ONE. Volume: 9
  • DOI: 10.1371/journal.pone.0103540
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effect of Asian sand dust on Japanese cedar pollinosis. (2014)
  • Author(s): Ogi K, Takabayashi T, Sakashita M, Susuki D, Yamada T, Manabe Y, Fujieda S.
  • Journal Title: Auris Nasus Larynx Volume: 41 Pages: 518-22
  • DOI: 10.1016/j.anl.2014.05.020
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Present state of Japanese cedar pollinosis : the national affliction (2014)
  • Author(s): Yamada T, Saito H, Fujieda S
  • Journal Title: J Allergy Clin Immunol. Volume: 133(3) Pages: 632-9
  • DOI: 10.1016/j.jaci.2013.11.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Guiding principles of subcutaneous immunotherapy for allergic rhinitis in Japan. Auris Nasus Larynx (2014)
  • Author(s): Okamoto Y, Ohta N, Okano M, et al
  • Journal Title: Auris Nasus Larynx Volume: 41(1) Pages: 1-5
  • DOI: 10.1016/j.anl.2013.06.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 舌下免疫療法の歴史とオーバービュー (2014)
  • Author(s): 藤枝重治
  • Journal Title: アレルギー・免疫 Volume: 21(7) Pages: 1085-1092
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 舌下免疫療法 (2014)
  • Author(s): 藤枝重治、坂下雅文、大澤陽子、意元義政
  • Journal Title: 耳喉頭頸 Volume: 86(1) Pages: 46-52
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] アレルギー性鼻炎の発症因子と先制医療 (2016)
  • Author(s): 藤枝重治
  • Organizer: 日本アレルギー学会第3回総合アレルギー講習会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-12-17
  • Invited
• [Presentation] アレルゲン免疫療法の期待と展望 (2016)
  • Author(s): 藤枝重治
  • Organizer: 第65回日本アレルギー学会学術大会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2016-06-17
  • Invited
• [Presentation] S. Fujieda, T. Ninomiya, Y. Imoto, Y. Kato, T. Tokunaga. (2015)
  • Author(s): Apolipoprotein A-IV is a new target molecule for allergic rhinitis.
  • Organizer: 13th Japan-Taiwan conference on Otolaryngology-Head and Neck Surgery
  • Place of Presentation: 東京
  • Year and Date: 2015-12-03
  • Int'l Joint Research / Invited
• [Presentation] S. Fujieda (2015)
  • Author(s): Apolipoprotein A-IV is a new target molecule for allergic rhinitis.
  • Organizer: 2015 Annual CORLAS Meeting
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] Apolipoprotein A-IV is a new target molecule for allergic rhinitis. (2015)
  • Author(s): S. Fujieda, T. Ninomiya, Y. Imoto, Y. Kato, S.
  • Organizer: European Academy of Allergy and Clinical Immunology Congress 2015
  • Place of Presentation: バルセロナ
  • Year and Date: 2015-06-06
  • Int'l Joint Research
• [Presentation] 舌下免疫療法の実際と対応 (2015)
  • Author(s): 藤枝重治
  • Organizer: 第116回日本耳鼻咽喉科学会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-21
• [Presentation] Apolipoprotein A-IV is a new target molecule for allergic rhinitis (2015)
  • Author(s): S. Fujieda
  • Organizer: 2015 International Congress of Korean Society of Otorhinolaryngology-
  • Place of Presentation: ソウル
  • Year and Date: 2015-04-24
  • Int'l Joint Research / Invited
• [Presentation] 花粉症と口腔アレルギー症候群 (2015)
  • Author(s): 藤枝重治
  • Organizer: 第78回日本皮膚科学会東京支部学術大会 モーニングセミナー
  • Place of Presentation: 東京 京王プラザ
  • Year and Date: 2015-02-22
  • Invited
• [Presentation] 小児アレルギー性鼻炎の問題点 (2014)
  • Author(s): 藤枝重治
  • Organizer: 第51回小児アレルギー学会 ランチョンセミナー
  • Place of Presentation: 四日市市 都ホテル
  • Year and Date: 2014-11-08
  • Invited
• [Presentation] Sublingeal immunotherapy for seasonal allergic rhinitis caused by Japnese cedar pollen. (2014)
  • Author(s): Fujieda S
  • Organizer: 15th Korea -Japan Joint meeting of Otolaryngology-Head and Neck Surgery
  • Place of Presentation: Seoul (Korea)
  • Year and Date: 2014-04-04