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Elucidation of the mechanism of chitinase-mediated airway inflammation by chitin

Research Project

Project/Area Number 21K08465
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionKyorin University

Principal Investigator

Arae Ken  杏林大学, 保健学部, 准教授 (50306669)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsキチン / アレルギー / 喘息 / 自然リンパ球
Outline of Research at the Start

アレルギー喘息の主要な要因はダニである。申請者は、ダニ外殻を構成する多糖類「キチン(Chitin)」をタンパク質抗原と同時に吸入させるとアレルギーが誘導され、その際にキチンによって誘導されるサイトカインIL-33の重要性を報告した。しかしながら、新たなダニアレルギー誘発物質「キチン」による気道炎症の誘導機構の全容は全く解明されていない。申請者は、キチンに結合する分子として可溶性タンパク質「Chil1」を同定し、Chil1とキチン粒子の複合体が、樹状細胞を活性化することを見出した。樹本申請では、キチン受容体の同定を含むキチン粒子による気道炎症誘発機構の解明を目指す。

Outline of Final Research Achievements

Chitin is a major component of the dust mite shell, and inhalation of it has been shown to induce airway inflammation and allergic asthma. Therefore, in this application, we aimed to elucidate the mechanism by which chitin particles induce airway inflammation. The results suggested that type 3 innate lymphoid cells (ILC3) may be strongly involved in chitin-induced airway inflammation. Furthermore, studies using newly established gene-deficient mice revealed that chitinase is strongly involved in airway inflammation caused by chitin. Furthermore, it was revealed that the main producing cells of chitinase are alveolar epithelial cells.

Academic Significance and Societal Importance of the Research Achievements

我が国では、アレルギー性気管支喘息やCOPD、突発性間質性肺炎といった慢性の炎症性呼吸器疾患が増加しており、大きな社会的及び医療経済的な問題となっている。これらの原因は不明ながら、環境因子による慢性気道炎症などが推測されている。このような環境要因の一つとして、ヒトの居住空間に豊富に存在し、ヒトが日常的に吸入しうる環境粒子キチン粒子を想定することができる。本申請によるキチン粒子による気道炎症誘導機構の解明は、原因不明な様々な慢性炎症性呼吸器疾患に対する予防薬や治療薬の新規創薬ターゲットの創出に貢献できると考えている。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (4 results)

All 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results)

  • [Int'l Joint Research] SIAF/CK-CARE(スイス)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Laundry detergents and surfactants induced eosinophilic airway inflammation by increasing IL-33 expression and activating ILC2s2023

    • Author(s)
      Saito K, Orimo K, Kubo T, Tamari M, Yamada A, Motomura K, Sugiyama H, Matsuoka R, Nagano N, Hayashi Y, Arae K, Hara M, Ikutani M, Fukuie T, Sudo K, Matsuda A, Ohya Y, Fujieda S, Saito H, Nakae S, Matsumoto K, Akdis CA, Morita H.
    • Journal Title

      Allergy

      Volume: - Issue: 7 Pages: 1878-1892

    • DOI

      10.1111/all.15762

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Infiltration of peripheral immune cells into the olfactory bulb in a mouse model of acute nasal inflammation.2022

    • Author(s)
      Asano H, Hasegawa-Ishii S*, Arae K, Obara A, Laumet G, Dantzer R and Shimada A.
    • Journal Title

      J Neuroimmunol.

      Volume: 368 Pages: 577897-577897

    • DOI

      10.1016/j.jneuroim.2022.577897

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Interleukin-33 and thymic stromal lymphopoietin, but not interleukin-25, are crucial for development of airway eosinophilia induced by chitin2021

    • Author(s)
      Arae Ken、Ikutani Masashi、Horiguchi Kotaro、Yamaguchi Sachiko、Okada Youji、Sugiyama Hiroki、Orimo Keisuke、Morita Hideaki、Suto Hajime、Okumura Ko、Taguchi Haruhiko、Matsumoto Kenji、Saito Hirohisa、Sudo Katsuko、Nakae Susumu
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 5913-5913

    • DOI

      10.1038/s41598-021-85277-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2021-04-28   Modified: 2025-01-30  

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