Study on the mechanisms of lung-mediated initiation of allergic diseases.

• Project/Area Number: 24790484
• 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, 助教 (20581549)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: IgE / MyD88 / B細胞 / 肺 / アレルギー / 花粉抗原 / アレルギー・ぜんそく / IgE産生 / 喘息 / Th2応答 / 抗体産生

Research Abstract

The production of immunoglobulin E (IgE) has a pivotal role in the development of allergic diseases including asthma. Although molecular mechanism underlying IgE class-switching in B cells has been well studied, how IgE production is induced in disease settings in our body is poorly understood. Previous studies regarding virus infection or autoimmunity reported the role of B-cell-intrinsic MyD88 signaling in Th1-type antibody responses, such as IgG2a/c production. However, the involvement of MyD88 signaling in Th2-type antibody, IgE/IgG1, responses has not been understood. Here, we studied on the IgE and IgG1 responses in intratracheally ragweed pollen exposed mice. We reveal that B-cell-intrinsic MyD88 is critical for IgE/IgG1 responses in pollen-exposed lungs in mice.

Research Products

• [Journal Article] Pathogenic Th2-type follicular helper T cells contribute to the development of lupus in Fas - deficient mice (2014)
  • Author(s): Futatsugi,. Yumikura S, Matsushita K, Fukuoka A, Takahashi S, Yamamoto N, Yonehara S, Nakanishi K, Yoshimoto T
  • Journal Title: Int. Immunol Volume: 26 Pages: 221-231
  • Peer Reviewed
• [Journal Article] Pathogenic Th2-type follicular helper T cells contribute to the development of lupus in Fas-deficient mice (2014)
  • Author(s): Futatsugi-Yumikura S, Matsushita K, Fukuoka A, Takahashi S, Yamamoto N, Yonehara S, Nakanishi K, Yoshimoto T
  • Journal Title: Int Immunol Volume: 26(4) Issue: 4 Pages: 221-231
  • DOI: 10.1093/intimm/dxt070
  • Peer Reviewed
• [Journal Article] Malt1-Induced Cleavage of Regnase-1 in CD4^+ Helper T Cells Regulates Immune Activation (2013)
  • Author(s): Uehata T, Iwasaki H, Vandenbon A, Matsushita K, Hernandez - Cuellar E, Kuniyoshi K, Satoh T, Mino T, Suzuki Y, Standley DM, Tsujimura T, Rakugi H, Isaka Y, Takeuchi O, Akira S
  • Journal Title: Cell Volume: 153 Pages: 1036-1049
  • Peer Reviewed
• [Journal Article] 顆粒球のアレルギー疾患におけるあらたな役割 (2013)
  • Author(s): 松下一史、善本知広
  • Journal Title: 実験医学増刊号 Volume: 31 Pages: 73-79
• [Journal Article] Malt1-Induced Cleavage of Regnase-1 in CD4+ Helper T Cells Regulates Immune Activation (2013)
  • Author(s): Uehata T, Iwasaki H, Vandenbon A, Matsushita, K, Hernandez Cuellar E, Kuniyoshi K, Satoh T, Mino T, Suzuki Y, Standley DM, Tsujimura T, Rakugi H, Isaka Y, Takeuchi O and Akira S
  • Journal Title: Cell Volume: 23;153 Issue: 5 Pages: 1036-49
  • DOI: 10.1016/j.cell.2013.04.034
  • Peer Reviewed
• [Journal Article] A critical role of IL-33 in experimental allergic rhinitis (2012)
  • Author(s): Haenuki Y, Matsushita K, Futatsugi-Yumikura S, Ishii KJ, Kawagoe T, Yasuda M, Hisa Y, Akira S, Nakanishi K, Yoshimoto T
  • Journal Title: J. Allergy Clin Immunol Volume: 130 Pages: 184-194
  • Peer Reviewed
• [Journal Article] A critical role of IL-33 in experimental allergic rhinitis (2012)
  • Author(s): Haenuki Y, Matsushita K, Futatsugi-Yumikura S, Ishii KJ, Kawagoe T, Imoto Y, Fujieda S, Yasuda M, Hisa Y, Akira S, Nakanishi K, Yoshimoto T
  • Journal Title: J Allergy Clin Immunol Volume: (in press) Issue: 1 Pages: 184-194
  • DOI: 10.1016/j.jaci.2012.02.013
  • Peer Reviewed
• [Journal Article] Contribution of IL-33-activated type II innate lymphoid cells to pulmonary eosinophilia in intestinal nematode-infected mice (2012)
  • Author(s): 安田好文, 他
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 109 Issue: 9 Pages: 3451-3456
  • DOI: 10.1073/pnas.1201042109
  • Peer Reviewed
• [Presentation] Pathogenic Th2-type follicular helper T cells contribute to the development of lupus in Fas-deficient mice (2013)
  • Author(s): Futatsugi-Yumikura S, Matsushita K, Fukuoka A, Takahashi S, Yamamoto N, Yonehara S, Nakanishi K, Yoshimoto T
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉(ワークショップ)
• [Presentation] BALB/c背景Fas-/-マウスで活性化された濾胞性ヘルパーT細胞はアレルギー疾患と自己免疫疾患を増悪させる (2013)
  • Author(s): 弓倉静英、高橋涼香、松下一史、福岡あゆみ、米原伸、中西憲司、善本知広
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
• [Presentation] Pathogenic Th2-type follicular helper T cells contribute to the development of lupus in Fas-deficient mice. (2013)
  • Author(s): Futatsugi-Yumikura S, Matsushita K, Fukuoka A, Takahashi S, Yamamoto N, Yonehara S, Nakanishi K, Yoshimoto T.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] BALB/c背景Fas-/-マウスで活性化された濾胞性ヘルパーT細胞はアレルギー疾患と自己免疫疾患を増悪させる. (2013)
  • Author(s): 弓倉静英、高橋涼香、松下一史、福岡あゆみ、米原伸、中西憲司、善本知広.
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
• [Presentation] Ragweed pollen-driven IL-33 contributes to the development of allergic rhinitis (2012)
  • Author(s): Haenuki Y, Matsushita K, Futatsugi-Yumikura S, Hisa Y, Akira S, Nakanishi K, Yoshimoto T
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸(ワークショップ)
• [Presentation] Contibution of IL-33-activated type II innate lymphoid cells to pulmonary eosinophilia in Strongyloides venezuelensis-infected mice (2012)
  • Author(s): Yasuda K, Muto T, Kawagoe T, Matsumoto M, Sasaki Y, Matsushita K, Futatsugi-Yumikura S, Tsutsui H, Ishi K, Yoshimoto T, Akira S, Nakanishi K
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸(ワークショップ)
• [Presentation] Chitin induces lung eosinophilia dependently on IL-33 (2012)
  • Author(s): Muto T, Yasuda K, Kawagoe T, Matsumoto M, Sasaki Y, Matsushita K, Futatsugi.. Yumikura S, Tsutsui H, Ishi K, Yoshimoto T, Akira S, Nakanishi K
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸(ワークショップ)
• [Presentation] Balb/c FasKO mice develop severe autoimmunity,allergy and highly achivated Tfh cells (2012)
  • Author(s): Futatsugi.. Yumikura S, Matsushita K, Fukuoka A, Yoshimoto T, Yonehara S, Nakanishi K
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸(ワークショップ)
• [Presentation] Akirin2 as a Conserved Nuclear Factor Involved in NF-kB Dependant Gene Expression in Inflammation (2012)
  • Author(s): Sarang T, Matsushita K, Takeuchi O, Akira S
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸(ワークショップ)
• [Presentation] Contribution of IL-33-activated type II innate lymphoid cells to pulmonary eosinophilia in intestinal nematode - infected mice (2012)
  • Author(s): Yasuda K, Muto T, Kawagoe T, Matsumoto M, Sasaki Y, Matsushita K, Taki Y, Futatsugi,. Yumikura S, Tsutsui H, Ishi K, Yoshimoto T, Akira S, Nakanishi K
  • Organizer: 第77回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 神戸
• [Presentation] A critical role of pollen – driven endogenous IL-33 in allergic rhinitis (2012)
  • Author(s): Yoshimoto T, Matsushita K, Haenuki Y, Futatsugi,. Yumikura S, Fujieda S, Hisa Y, Akira S, Nakanishi K
  • Organizer: EAACI Congress
  • Place of Presentation: Switzerland(Guest Speech)
• [Presentation] A critical role of pollen–driven endogenous IL-33 in allergic rhinitis. (2012)
  • Author(s): Yoshimoto T, Matsushita K, Haenuki Y, Futatsugi-Yumikura S, Fujieda S, Hisa Y, Akira S, Nakanishi K.
  • Organizer: European Academy of Allergy and Clinical Immunology (EAACI Congress 2012)
  • Place of Presentation: Geneva/Switzerland
• [Presentation] Ragweed pollen-driven IL-33 contributes to the development of allergic rhinitis. (2012)
  • Author(s): Haenuki Y, Matsushita K, Futatsugi-Yumikura S, Hisa Y, Akira S, Nakanishi K, Yoshimoto T.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Contibution of IL-33-activated type II innate lymphoid cells to pulmonary eosinophilia in Strongyloides venezuelensis-infected mice. (2012)
  • Author(s): Yasuda K, Muto T, Kawagoe T, Matsumoto M, Sasaki Y, Matsushita K, Futatsugi-Yumikura S, Tsutsui H, Ishi K, Yoshimoto T, Akira S, Nakanishi K.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Chitin induces lung eosinophilia dependently on IL-33. (2012)
  • Author(s): Muto T, Yasuda K, Kawagoe T, Matsumoto M, Sasaki Y, Matsushita K, Futatsugi-Yumikura S, Tsutsui H, Ishi K, Yoshimoto T, Akira S, Nakanishi K.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Balb/c FasKO mice develop severe autoimmunity,allergy and highly achivated Tfh cells. (2012)
  • Author(s): Futatsugi-Yumikura S, Matsushita K, Fukuoka A, Yoshimoto T, Yonehara S, Nakanishi K.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] Akirin2 as a Conserved Nuclear Factor Involved in NF-kB Dependant Gene Expression in Inflammation. (2012)
  • Author(s): 5. Sarang T, Matsushita K, Takeuchi O, Akira S.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Book] A multifunctional alarmin that promotes both health and disease. Cytokine Frontiers : Regulation of Immune Responses in Health and Disease. Interleukin - 33 (2014)
  • Author(s): Matsushita K, Yoshimoto T
  • Publisher: Springer, New York
• [Book] Cytokine Frontiers: Regulation of Immune Responses in Health and Disease. (2014)
  • Author(s): Matsushita K, Yoshimoto T.
  • Publisher: Springer