Mechanism of sublingual immunotherapy -experimental approach in murine model-

2013 Fiscal Year Final Research Report

• Project/Area Number: 23659796
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Shimane University
• Principal Investigator: KAWAUCHI Hideyuki 島根大学, 医学部, 教授 (50161279)
• Co-Investigator(Kenkyū-buntansha): MORIKURA Ichiro 島根大学, 医学部, 助教 (00362939) ; AOI Noriaki 島根大学, 医学部, 講師 (80452556)
• Project Period (FY): 2011 – 2013
• Keywords: アレルギー性鼻炎 / ｽｷﾞ花粉症 / ｽｷﾞ花粉症治療米 / 舌下免疫療法 / regulatory T cells / ＩｇＥ抗体

Research Abstract

To elucidate the mechanism of sublingual immunotherapy for allergic rhinitis, we have successfully constructed murine allergic rhinitis model with ovalbumin or cedar pollen as allergens. In this murine model, we demonstrated that sublingual immunotherapy at an induction phase actually attenuates nasal symptoms such as sneezing and nasal rubbing by downregulating allergen-specific IgE in sera. Moreover, allergen-specific regulatory T cells were induced in the cervical lymph node of mice sublingually immunized and these cells singnificantly produced IL-10
in an antigen-specific fashion.

Research Products

• [Journal Article] SCUAD and chronic rhinosinusitis. Reinforcing hypothesis driven research in difficult cases (2014)
  • Author(s): Emmanuel P. Prokopakis, Ioannis M. Vlastos, Berrylin J. Ferguson, Glenis Scadding, Hideyuki Kawauchi, Christos Georgalas, Nikolaos Papadopoulos, Peter W. Hellings
  • Journal Title: Rhinology Volume: 52 Pages: 3-8
• [Journal Article] マウス舌下免疫療法モデルにおける頸部リンパ節IL-10産生制御性T細胞の誘導 (2013)
  • Author(s): 屈銀斐、頓宮美樹、田村優希江、山田高也、青井典明、森倉一朗、淵脇貴史、川内秀之
  • Journal Title: 耳鼻免疫アレルギー Volume: 31(2) Pages: 49-50
• [Journal Article] Oral Administration of Fexofenadine Hydrochloride can Attenuate Nasal Symptoms and Restore the Impaired Cognitive Function in School-Age Patients With Japanese Cedar Pollinosis (2013)
  • Author(s): Noriaki AOI, Yasuhiko SHIMIZU, Ichiro MORIKURA, Knanako SHIMIZU, Takafumi FUCHIWAKI, Yukie TAMURA, Keisuke SANO, Mitsuhiro KIMURA, Akemichi MURATA, Hideyuki KAWAUCHI
  • Journal Title: Shimane J. Med. Sci Volume: Vol.29 Pages: 79-86
• [Journal Article] Metronomic chemotherapy with low-dose cyclophosphamide plus gemcitabine can induce anti-tumor T cell immunity in vivo (2013)
  • Author(s): Miki Tongu, Nanae Harashima, Hiroyuki Monma, Touko Inao, Takaya Yamada, Hideyuki Kawauchi, Mamoru Harada
  • Journal Title: Cancer Immunology and Immunotherapy Volume: 62 Pages: 383-391
• [Journal Article] The pathophysiology of the hygiene hypothesis (2013)
  • Author(s): Emmanuel Prokopakis, Alexios Vardouniotis,Hideyuki Kawauchi, Glenis Scadding, Christos Georgalas, Peter Hellings, George Velegrakis,Livije Kalogjera
  • Journal Title: International Journal of Pediatric otorhinolaryngolory Volume: 77 Pages: 1065-1071
• [Journal Article] Effects of the Japanese traditional medicine Bu-zhong-yi-qi-tang on Th2 responsesvia up-regulation of Toll-like receptor 4 (2013)
  • Author(s): Yasuhiko Shimizu, Noriaki Aoi, Ichiro Morikura, Takafumi Fuchiwaki, Hideyuki Kawauchi
  • Journal Title: ARSR Journal 2013
• [Journal Article] Sublingual immunotherapy induces regulatory function of IL-10 expressing CD4^+CD25^+Foxp^<3+> T cells of cervical lymph nodes in murine allergic rhinitis model (2012)
  • Author(s): Takaya Yamada, Miki Tongu, Kaoru Goda, Noriaki Aoi, Ichiro Morikura, Takafumi Fuchiwaki and Hideyuki Kawauchi
  • Journal Title: J Allergy Volume: (Article ID 490905) Pages: 11
  • DOI: 10.1155/2012/490905
• [Journal Article] Metronomic chemotherapy with low-dose cyclophosphamide plus gemcitabine can induce anti-tumor T cell immunity in vivo (2012)
  • Author(s): Miki Tongu, Nanae Harashima, Hiroyuki Monma, Touko Inao, Takaya Yamada, Hideyuki Kawauchi, Mamoru Harada
  • Journal Title: Cancer Immunol Immunother
  • DOI: 10.1007/s00262-012-1343-0
• [Journal Article] Prevention of lung injury by Muc1 mucin in a mouse model of repetitive Pseudomonas aeruginosa infection (2012)
  • Author(s): Tsuyoshi Umehara, Kosuke Kato, Yong Sung Park, Erik P Lillehoj, Hideyuki Kawauchi, Kwang Chul Kim
  • Journal Title: Inflammation research
  • DOI: 10.1007/s00011-012-0494-y
• [Journal Article] Examination, diagnosis and classification for Japanese allergic rhinitis : Japanese guideline (2012)
  • Author(s): Yuichi Kurono, Kimihiro Okubo, Keiichi Ichimura, Tadao Enomoto, Hideyuki Kawauchi, Keisuke Masuyama, Minoru Goto, Harumi Suzaki, Yoshitaka Okamoto, Hiroshi Takenaka
  • Journal Title: Auris, nasus, larynx Volume: 39(6) Pages: 553-556
• [Journal Article] Canalith repositioning procedures among 965 patients with benign paroxysmal positional vertigo (2012)
  • Author(s): Prokopakis E, Vlatos IM, Tsagournisakis M, Christodoulou P, Kawauchi H, Velegrakis G
  • Journal Title: Audiol Neurotol
  • DOI: 10.1159/000343579
• [Journal Article] Short review on sublingual immunotherapy for patients with allergic rhinitis : from bench to bedside (2011)
  • Author(s): Hideyuki Kawauchi, Kaoru Goda, Miki Tongu, Takaya Yamada, Noriaki Aoi, Ichiro Morikura, Takashi Fuchiwaki
  • Journal Title: Advances in Oto-Rhino-Laryngology Volume: 72 Pages: 103-6
• [Journal Article] The central role of CD30L/CD30 interactions in allergic rhinitis pathogenesis in mice (2011)
  • Author(s): Takafumi Fuchiwaki, Xun Sun, Kenjiro Fujimura, Hisakata Yamada, Kensuke Shibata, Hiromi Muta, Eckhard R Podack, Hideyuki Kawauchi, Yasunobu Yoshikai
  • Journal Title: Eur J Immunol Volume: 41 Pages: 2947-2954
• [Journal Article] Japanese traditional medicine, Senn-kinn-naidaku-sann up-regulates Toll-like receptor 4 and reduces murine allergic rhinitis
  • Author(s): Ichiro Morikura, Akemichi Murata, Hisashi Ohga, Kaoru Goda, Noriaki Aoi, Shingo Kataoka, Hideyuki Kawauchi
  • Journal Title: Rhinology Volume: (in press)
• [Presentation] Sublingual immunotherapy with a rice-based vaccine expressing cedar pollen multiple Tcell epitopes attenuates nasal sympotoms in murine allergic rhinitis model with pollinosis (2013)
  • Author(s): Hideyuki Kawauchi
  • Organizer: 16th Asian Research Symposium in Rhinology
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20130829-31
• [Presentation] マウスアレルギー性鼻炎モデルにおける舌下免疫療法の有用性と機序の検討 (2013)
  • Author(s): 屈銀斐、田村優希江、山田高也、青井典明、森倉一朗、淵脇貴史、川内秀之
  • Organizer: 第52回日本鼻科学会総会・学術講演会
  • Place of Presentation: 福井市
  • Year and Date: 2013-09-28
• [Presentation] マウス舌下免疫療法モデルにおける頸部リンパ節IL-10 産生制御性T 細胞の誘導 (2013)
  • Author(s): 屈銀斐、田村優希江、青井典明、森倉一朗、淵脇貴史、川内秀之
  • Organizer: 日本耳鼻咽喉科学会第39回中国四国地方部会連合学会
  • Place of Presentation: 高知
  • Year and Date: 2013-05-25
• [Presentation] Sublingual immunotherapy induces regulatory function of IL-10 expressing CD4^+ CD25^+ Foxp3^+ T cells of cervical lymph nodes and actually attenuates nasal symptoms upon allergen exposure in murine allergic rhinitis model (2013)
  • Author(s): Yin Fei Qu, Miki Tongu, Yukie Tamura, Takaya Yamada, Noriaki Aoi, Ichiro Morikura, Takafumi Fuchiwaki, Hideyuki Kawauchi
  • Organizer: 第31回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 倉敷市
  • Year and Date: 2013-02-08
• [Presentation] スギ花粉症治療米の舌下投与によるマウススギ花粉症モデルでの症状抑制効果の検討 (2012)
  • Author(s): 川内秀之,屈銀斐,頓宮美樹,山田高也,田村優希江,青井典明,淵脇貴史
  • Organizer: 第51回日本鼻科学会総会・学術講演会
  • Place of Presentation: 千葉市
  • Year and Date: 2012-09-29
• [Presentation] Sublingual immunotherapy with a rice-based edible vaccine expressing cedar pollen multiple T cell epitopes attenuates the nasal symptoms in murine allergic rhinitis model with pollinosis (2012)
  • Author(s): Hideyuki Kawauchi
  • Organizer: 24^<th> ERS - 31^<st> ISIAN
  • Place of Presentation: Toulouse, France
  • Year and Date: 2012-06-19
• [Presentation] Mucosal immunity of the pasopharynx and its clinical application for downregulating allergic thinitis (2012)
  • Author(s): Hideyuki Kawauchi
  • Organizer: 24th ]ERS - 31^<st> ISIAN
  • Place of Presentation: Toulouse, France
  • Year and Date: 2012-06-19
• [Presentation] Sublingual immunotherapy with a rice-based edible vaccine expressing cedar pollen multiple T cell epitopes attenuates the nasal symptoms in murine allergic rhinitis model with pollinosis (2012)
  • Author(s): Kawauchi, H, Yamada T, Tongu M, Aoi, N, Takagi H, Takaiwa F
  • Organizer: European Academy of Allergy and Clinical Immunology Congress 2012 Geneve
  • Place of Presentation: Switzerland
  • Year and Date: 2012-06-17
• [Presentation] Mucosa immunity of nasopharynx and its clinical impact (2012)
  • Author(s): Hideyuki Kawauchi
  • Organizer: 15^<th> ASIAN RESEARCH SYMPOSIUM IN RHINOLOGY
  • Place of Presentation: Singapore
  • Year and Date: 2012-05-25
• [Presentation] アレルギー性鼻炎におけるCD30 ligand の役割 (2012)
  • Author(s): 淵脇貴史,孫遜,吉開泰信,川内秀之
  • Organizer: 第113回日本耳鼻咽喉 科学会総会・学術講演会
  • Place of Presentation: 新潟市
  • Year and Date: 2012-05-12
• [Presentation] アレルギー性鼻炎におけるCD30 ligand の役割 (2012)
  • Author(s): 淵脇貴史,森倉一朗,青井典明,吉開泰信,川内秀之
  • Organizer: 第30回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 大津市
  • Year and Date: 2012-02-18
• [Presentation] マウス用スギ花粉治療米を用いた舌下免疫療法の有効性の検討 (2011)
  • Author(s): 川内秀之,山田高也,頓宮美樹,青井典明,森倉一朗,淵脇貴史,高岩文雄
  • Organizer: 第61回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京都
  • Year and Date: 2011-11-12
• [Presentation] Eosinophilic Rhinosinusitis in Japan (2011)
  • Author(s): Hideyuki Kawauchi
  • Organizer: 6^<th> International Consensus Conference on Nasal Polyposis
  • Place of Presentation: Kiev, Ukraina
  • Year and Date: 2011-09-26
• [Presentation] The Role of Toll-like Receptors in the Sinonasal Allergic and Infective Inflammation (2011)
  • Author(s): Hideyuki Kawauchi
  • Organizer: 6^<th> International Consensus Conference on Nasal Polyposis
  • Place of Presentation: Kiev
  • Year and Date: 2011-09-26
• [Presentation] Nasal Mucosal Immunology and its Clinical Impact -Experimental Skills for Rhinologists- (2011)
  • Author(s): Hideyuki Kawauchi
  • Organizer: IRS & ISIAN 2011
  • Place of Presentation: Tokyo
  • Year and Date: 2011-09-22
• [Presentation] Mucosal Immunity of Nasopharynx and its Clinical Application for AR & Infections Disease (2011)
  • Author(s): Hideyuki Kawauchi
  • Organizer: IRS & ISIAN 2011
  • Place of Presentation: Tokyo
  • Year and Date: 2011-09-21
• [Presentation] The Central Role of CD30L/CD30 Interactions in Allergic Rhinitis Pathogenesis in Mice (2011)
  • Author(s): Takafumi Fuchiwaki, Xun Sun, Noriaki Aoi, Yasunobu Yoshikai, Hideyuki Kawauchi
  • Organizer: IRS & ISIAN 2011
  • Place of Presentation: Tokyo
  • Year and Date: 2011-09-21
• [Presentation] マウスアレルギー性鼻炎モデルを用いた舌下免疫療法の有効性と作用機序の検討 (2011)
  • Author(s): 川内秀之,青井典明
  • Organizer: 第23回日本アレルギー学会春季臨床大会
  • Place of Presentation: 千葉市
  • Year and Date: 2011-05-14
• [Book] Macrophage, Nasal Physiology and pathophysiology of Nasal Disorders, Edited by Metin Onerci (2013)
  • Author(s): Hideyuki Kawauchi
  • Total Pages: 77-88
  • Publisher: Splinger-Verlag Berlin Heidelberg
• [Book] Nasal Defensive Proteins : Distribution and a Biological Function, Nasal Physiology and pathophysiology of Nasal Disorders, Edited by Metin Onerci (2013)
  • Author(s): Hideyuki Kawauchi
  • Total Pages: 395-402
  • Publisher: Splinger-Verlag Berlin Heidelberg