Analysis of signal transduction mechanisms by chitin through Chitinase-like proteins.

2016 Fiscal Year Annual Research Report

• Project/Area Number: 16K15515
• Research Institution: National Center for Child Health and Development
• Principal Investigator: 斎藤 博久 国立研究開発法人国立成育医療研究センター, 副所長室, 副所長 (40130166)
• Project Period (FY): 2016-04-01 – 2017-03-31
• Keywords: キチン / アレルギー

Outline of Annual Research Achievements

ダニは最も主要なアレルゲンであるが、そのアレルギー誘導機構は不明である。申請者は、マウスにおいて、タンパク質抗原単独ではアレルギー応答は誘導されないが、ダニの外殻構成成分「キチン（Chitin）」の存在下では、Type-2サイトカイン誘導因子であるIL-33の発現誘導を介して、IL-4/13－STAT6経路依存的なアレルギー応答が誘導されることを見出した。キチンのこの効果には、新規のキチン受容体の関与が想定され、これまでに、キチン結合タンパク質としてキチナーゼ様タンパク質「Chil1」をマウス肺より同定している。Chil1は、キチン吸入による気道炎症の増強や、キチン存在下での樹状細胞によるサイトカイン産生を誘導することから、キチンによるアレルギー誘導に関わると考えられる。本申請では、Chil1下流分子の新規同定を目指した。
今回、固相化Chil1タンパク質を用いたpanning法による同定を試みた。COS-7細胞にplasmid型の発現ベクターを用いたマウス肺cDNAライブラリーを、リポフェクション法により遺伝子導入する。強制発現後、固相化したChil1に結合するCOS-7クローンをpanning法により選び出し、含まれるplasmidベクターのインサートDNAの塩基配列から、Chil1結合タンパク質を同定するというものである。その結果、アデニル酸シクラーゼやATP合成酵素のような酵素、プラコグロビンやダイニンなど細胞の構造タンパク質、さらにはアペリンやサイモシンなどの生理活性物質等、様々なインサートDNAが同定された。しかしながら、同定される分子に再現性がなく、panning法により選抜されるクローンは、固相化Chil1もしくは固相に非特異的に結合しているに過ぎないと考えられ、スクリーニング法の変更が必要であると考えられた。

Research Products

• [Int'l Joint Research] SIAF(Switzerland)
  • Country Name: Switzerland
  • Counterpart Institution: SIAF
• [Int'l Joint Research] Stanford University School of Medicine/Departments of Pathology(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: Stanford University School of Medicine/Departments of Pathology
• [Int'l Joint Research] Cambridge/MRC Laboratory of Molecular Biology(英国)
  • Country Name: UNITED KINGDOM
  • Counterpart Institution: Cambridge/MRC Laboratory of Molecular Biology
• [Journal Article] Human eosinophils constitutively express a unique serine protease, PRSS33. (2017)
  • Author(s): Toyama S, Okada N, Matsuda A, Morita H, Saito H, Fujisawa T, Nakae S, Karasuyama H, Matsumoto K.
  • Journal Title: Allergol Int Volume: In Press Pages: In Press
  • DOI: 10.1016/j.alit.2017.01.001
  • Peer Reviewed / Open Access
• [Journal Article] Yogurt consumption in infancy is inversely associated with atopic dermatitis and food sensitization at 5 years of age: A hospital-based birth cohort study. (2017)
  • Author(s): Shoda T, Futamura M, Yang L, Narita M, Saito H, Ohya Y.
  • Journal Title: J Dermatol Sci Volume: 86 Pages: 90-6
  • DOI: 10.1016/j.jdermsci.2017.01.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development of chronic allergic responses by dampening Bcl6-mediated suppressor activity in memory T helper 2 cells. (2017)
  • Author(s): Ogasawara T, Hatano M, Satake H, Ikari J, Taniguchi T, Tsuruoka N, Watanabe-Takano H, Fujimura L, Sakamoto A, Hirata H, Sugiyama K, Fukushima Y, Nakae S, Matsumoto K, Saito H, Fukuda T, Kurasawa K, Tatsumi K, Tokuhisa T, Arima M.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 114 Pages: E741-E50
  • DOI: 10.1073/pnas.1613528114
  • Peer Reviewed
• [Journal Article] Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. (2017)
  • Author(s): Natsume O, Kabashima S, Nakazato J, Yamamoto-Hanada K, Narita M, Kondo M, Saito M, Kishino A, Takimoto T, Inoue E, Tang J, Kido H, Wong GW, Matsumoto K, Saito H, Ohya Y.
  • Journal Title: Lancet Volume: 389 Pages: 276-86
  • DOI: 10.1016/S0140-6736(16)31418-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] IL-33 in clinical practice: size matters? (2017)
  • Author(s): Morita H, Nakae S, Saito H, Matsumoto K.
  • Journal Title: J Allergy Clin Immunol Volume: Accepted Pages: Accepted
  • DOI: 10.1016/j.jaci.2017.03.042
  • Peer Reviewed
• [Journal Article] Preconceptional exposure to oral contraceptive pills and the risk of wheeze, asthma and rhinitis in children. (2016)
  • Author(s): Yamamoto-Hanada K, Futamura M, Yang L, Shoda T, Narita M, Kobayashi F, Saito H, Ohya Y.
  • Journal Title: Allergol Int Volume: 65 Pages: 327-31
  • DOI: 10.1016/j.alit.2016.02.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Platelets constitutively express IL-33 protein and modulate eosinophilic airway inflammation. (2016)
  • Author(s): Takeda T, Unno H, Morita H, Futamura K, Emi-Sugie M, Arae K, Shoda T, Okada N, Igarashi A, Inoue E, Kitazawa H, Nakae S, Saito H, Matsumoto K, Matsuda A.
  • Journal Title: J Allergy Clin Immunol Volume: 138 Pages: 1395-403
  • DOI: 10.1016/j.jaci.2016.01.032
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sera of patients with infantile eosinophilic gastroenteritis showed a specific increase in both thymic stromal lymphopoietin and IL-33 levels. (2016)
  • Author(s): Shoda T, Matsuda A, Arai K, Shimizu H, Morita H, Orihara K, Okada N, Narita M, Ohya Y, Saito H, Matsumoto K, Nomura I.
  • Journal Title: J Allergy Clin Immunol Volume: 138 Pages: 299-303
  • DOI: 10.1016/j.jaci.2015.11.042
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Timing of eczema onset and risk of food allergy at 3 years of age: A hospital-based prospective birth cohort study. (2016)
  • Author(s): Shoda T, Futamura M, Yang L, Yamamoto-Hanada K, Narita M, Saito H, Ohya Y.
  • Journal Title: J Dermatol Sci Volume: 84 Pages: 144-8
  • DOI: 10.1016/j.jdermsci.2016.08.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Recent advances in understanding the roles of vascular endothelial cells in allergic inflammation. (2016)
  • Author(s): Shoda T, Futamura K, Orihara K, Emi-Sugie M, Saito H, Matsumoto K, Matsuda A.
  • Journal Title: Allergol Int Volume: 65 Pages: 21-9
  • DOI: 10.1016/j.alit.2015.08.001
  • Peer Reviewed / Open Access
• [Journal Article] Regulatory roles of mast cells in immune responses. (2016)
  • Author(s): Morita H, Saito H, Matsumoto K, Nakae S.
  • Journal Title: Semin Immunopathol Volume: 38 Pages: 623-9
  • DOI: 10.1007/s00281-016-0566-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Comparison of Self-Rated and Female Partner-Rated Scales in the Assessment of Paternal Prenatal Depression. (2016)
  • Author(s): Konishi M, Tachibana Y, Tang J, Takehara K, Kubo T, Hashimoto K, Kitazawa H, Saito H, Ohya Y.
  • Journal Title: Community Ment Health J Volume: 52 Pages: 983-8
  • DOI: 10.1007/s10597-015-9931-z
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Transepidermal water loss measurement during infancy can predict the subsequent development of atopic dermatitis regardless of filaggrin mutations. (2016)
  • Author(s): Horimukai K, Morita K, Narita M, Kondo M, Kabashima S, Inoue E, Sasaki T, Niizeki H, Saito H, Matsumoto K, Ohya Y.
  • Journal Title: Allergol Int Volume: 65 Pages: 103-8
  • DOI: 10.1016/j.alit.2015.09.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] INTERLEUKIN-33 IN ALLERGIC DISEASES. (2016)
  • Author(s): Arae K, Morita H, Matsumoto K, Saito H, Nakae S.
  • Journal Title: Arerugi Volume: 65 Pages: 1269-76
  • DOI: 10.15036/arerugi.65.1269
  • Peer Reviewed / Open Access / Int'l Joint Research