A study on Th2 and IgE responses in the airway allergic diseases.

• Project/Area Number: 26860340
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Hyogo Medical University
• Principal Investigator: Matsushita Kazufumi 兵庫医科大学, 医学部, 講師 (20581549)
• Research Collaborator: YOSHIMOTO TOMOHIRO 兵庫医科大学, 医学部, 教授 (60241171)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: IgE / Th2 / 気道 / アレルギー / IL-33 / TSLP / エンドトキシン

Outline of Final Research Achievements

We investigated the mechanisms underlying IgE responses induced by particulate allergen exposure in lungs. We showed that B-cell-intrinsic MyD88 signaling activated by endogenous ligands, IL-1α, IL-1β, and IL-18, played a critical role in the antigen-specific IgE responses in lungs exposed to pollen allergens.
In addition, we investigated a novel role of Th2 cells in allergic airway diseases. Using an OVA-specific Th2 cells adoptive transfer model, we found that nasal CD4+ T cell activation followed by endotoxin exposure elicited IgE-independent rhinitis symptoms. This study shows the presence of T-cell-dependent and non-IgE-mediated nasal hypersensitivity-like reaction in mice.

Research Products

• [Journal Article] Allergen endotoxins induce T cell-dependent and non-IgE-mediated nasal hypersensitivity in mice. (2016)
  • Author(s): Iwasaki N, Matsushita K, Fukuoka A, Nakahira M, Matsumoto M, Akasaki S, Yasuda K, Shimizu T, Yoshimoto T.
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: -
  • Peer Reviewed / 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: International Immunology Volume: 28 Issue: 2 Pages: 65-76
  • DOI: 10.1093/intimm/dxv055
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Diesel exhaust particles exacerbate allergic rhinitis in mice by disrupting the nasal epithelial barrier. (2016)
  • Author(s): Fukuoka A, Matsushita K, Morikawa T, Takano H, Yoshimoto T.
  • Journal Title: Clinical&Experimental Allergy Volume: 46 Issue: 1 Pages: 142-152
  • DOI: 10.1111/cea.12597
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Essential function for the nuclear protein Akirin2 in B cell activation and humoral immune responses. (2015)
  • Author(s): Tartey S, Matsushita K, Imamura T, Wakabayashi A, Ori D, Mino T, Takeuchi O.
  • Journal Title: The Journal of Immunology Volume: 195 Issue: 2 Pages: 519-527
  • DOI: 10.4049/jimmunol.1500373
  • Peer Reviewed
• [Journal Article] Proallergic cytokines and group 2 innate lymphoid cells in allergic nasal diseases (2015)
  • Author(s): Kazufumi Matsushita , Yukinori Kato , Shoko Akasaki , Tomohiro Yoshimoto
  • Journal Title: Allergology International Volume: 64 Issue: 3 Pages: 235-240
  • DOI: 10.1016/j.alit.2014.12.008
  • NAID: 130005290321
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] IL-33による感染症防御 (2015)
  • Author(s): 松下一史、善本知広
  • Journal Title: 医学のあゆみ Volume: 252 Pages: 1215-1220
• [Journal Article] B cell-Intrinsic MyD88 signaling Is essential for IgE responses in lungs exposed to pollen allergens (2014)
  • Author(s): Matsushita K, Yoshimoto T.
  • Journal Title: The Journal of Immunology Volume: 193 Issue: 12 Pages: 5791-800
  • DOI: 10.4049/jimmunol.1401768
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex (2014)
  • Author(s): Sarang Tartey, Kazufumi Matsushita, Alexis Vandenbon, Daisuke Ori, Tomoko Imamura, Takashi Mino, Daron M. Standley, Jules A. Hoffmann, Jean-Marc Reichhart, Shizuo Akira, Osamu Takeuchi
  • Journal Title: The EMBO Journal Volume: 33 Issue: 20 Pages: 2332-2348
  • DOI: 10.15252/embj.201488447
  • NAID: 120005649311
  • Peer Reviewed
• [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 Issue: 8 Pages: e103540-e103540
  • DOI: 10.1371/journal.pone.0103540
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of basophilis and pro-allergic cytokines TSLP and IL-33, in cutaneously-sensitized food allergy (2014)
  • Author(s): Muto T, Fukuoka A, Kabashima i, Steven F. Z, Nakanishi K, Matsushita K, Yoshimoto T
  • Journal Title: International Immunology Volume: 26 Issue: 10 Pages: 539-49
  • DOI: 10.1093/intimm/dxu058
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Hypertrophy of lymphoid organs is a possible phenotypic characteristic of R420W mutation of the cardiac ryanodine receptor gene: A study using a knock-in mouse model. (2014)
  • Author(s): Nishio H, Okudaira N, Matsushita K, Yoshimoto T, Sato T, Suzuki K.
  • Journal Title: Legal Medicine Volume: 16 Issue: 6 Pages: 326-32
  • DOI: 10.1016/j.legalmed.2014.06.008
  • Peer Reviewed
• [Journal Article] Innate-Type and Acquired-Type Allergy Regulated by IL-33 (2014)
  • Author(s): Yoshimoto T, Matsushita K
  • Journal Title: Allergology International Volume: 63 Issue: Supplement.1 Pages: S3-S11
  • DOI: 10.2332/allergolint.13-RA-0657
  • NAID: 130004477232
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] B-cell-intrinsic MyD88 signaling is essential for IgE responses in lungs exposed to pollen allergens. (2015)
  • Author(s): Matsushita K, Yoshimoto T.
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター (北海道、札幌)
  • Year and Date: 2015-11-18
• [Presentation] Diesel exhaust particles exacerbate allergic rhinitis in mice by disrupting the nasal epithelial barrier. (2015)
  • Author(s): Fukuoka A, Matsushita K, Morikawa T, Takano H, Yoshimoto T.
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター (北海道、札幌)
  • Year and Date: 2015-11-18
• [Presentation] Murine allergic rhinitis and nasal Th2 activation are mediated via TSLP- and IL-33-signaling pathways. (2015)
  • Author(s): Akasaki S, Matsushita K, Yoshimoto T.
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター (北海道、札幌)
  • Year and Date: 2015-11-18
• [Presentation] Endotoxin containing allergens induce T cell-dependent non-IgE-mediated nasal hypersensitivity in mice. (2015)
  • Author(s): Iwasaki N, Matsushita K, Yoshimoto T.
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター (北海道、札幌)
  • Year and Date: 2015-11-18
• [Presentation] 肺への花粉抗原暴露によるIgE産生誘導におけるIL-1ファミリーサイトカインとＢ細胞特異的MyD88シグナル伝達の役割 (2015)
  • Author(s): 松下一史、善本知広
  • Organizer: 第80回日本インターフェロンサイトカイン学会
  • Place of Presentation: グランドプリンスホテル新高輪 (東京)
  • Year and Date: 2015-07-17
  • Invited
• [Presentation] 気道への花粉曝露によるIL-1ファミリーサイトカインを介した抗原特異的IgEの誘導 (2015)
  • Author(s): 松下一史、善本知広.
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: 東京工業大学 (東京)
  • Year and Date: 2015-05-26
  • Invited
• [Presentation] アレルギー性鼻炎モデルマウスにおけるTSLPの役割 (2015)
  • Author(s): 赤崎晶子、加藤幸宣、松下一史、善本知広．
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪 (東京)
  • Year and Date: 2015-05-26
• [Presentation] ディーゼル排気粒子がアレルギー性鼻炎に与える影響 (2015)
  • Author(s): 福岡あゆみ、松下一史、高野裕久、善本知広．
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪 (東京)
  • Year and Date: 2015-05-26
• [Presentation] LPSを引き金としたIgE非依存性鼻炎症状の誘導 (2015)
  • Author(s): 岩崎成仁、松下一史、清水猛史、善本知広．
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪 (東京)
  • Year and Date: 2015-05-26
• [Presentation] Essential role of B-cell-intrinsic MyD88-signaling in IgE responses in lungs. (2015)
  • Author(s): Matsushita K, Yoshimoto T.
  • Organizer: AAAAI 2015 Annual Meeting.
  • Place of Presentation: Houston, USA.
  • Year and Date: 2015-02-20 – 2015-02-24
• [Presentation] Diesel Exhaust Particles Exacerbate Allergic Rhinitis in Mice By Disrupting the Nasal Epithelial Barrier. (2015)
  • Author(s): Fukuoka A, Matsushita K, Takano H, Yoshimoto T.
  • Organizer: AAAAI 2015 Annual Meeting.
  • Place of Presentation: Houston, USA.
  • Year and Date: 2015-02-20 – 2015-02-24
• [Presentation] The Role of Basophils and Pro-Allergic Cytokines, TSLP and IL-33, in Cutaneously-Sensitized Food Allergy. (2015)
  • Author(s): Muto T, Fukuoka A, Matsushita K, Yoshimoto T.
  • Organizer: AAAAI 2015 Annual Meeting.
  • Place of Presentation: Houston, USA.
  • Year and Date: 2015-02-20 – 2015-02-24
• [Presentation] Essential role of B-cell-intrinsic MyD88-signaling in IgE responses in lungs. (2014)
  • Author(s): Matsushita K, Yoshimoto T.
  • Organizer: Cell Symposia, The Multifaceted Roles of Type 2 Immunity.
  • Place of Presentation: Brugge, Belgium.
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] 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.
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] The Role of Basophils and Pro-Allergic Cytokines, TSLP and IL-33, in Cutaneously-Sensitized Food Allergy. (2014)
  • Author(s): Muto T, Fukuoka A, Matsushita K, Yoshimoto T.
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] 肺への抗原曝露によるIgE産生誘導におけるB細胞特異的MyD88シグナル伝達の役割 (2014)
  • Author(s): 松下一史、善本知広.
  • Organizer: 第79回日本インターフェロン・サイトカイン学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2014-06-19 – 2014-06-20
• [Presentation] ブタクサ花粉の経鼻感作によるlocal allergic rhinitis (LAR)の誘導 (2014)
  • Author(s): 赤崎晶子、加藤幸宣、松下一史、善本知広
  • Organizer: 第79回日本インターフェロン・サイトカイン学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2014-06-19 – 2014-06-20