Chitin-mediated IL-33 induces breakdown of immune tolerance by excessive IL-1b production by DCs, causing aggravation of murine asthma

• Project/Area Number: 26461491
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyorin University
• Principal Investigator: Arae Ken 杏林大学, 保健学部, 講師 (50306669)
• Co-Investigator(Renkei-kenkyūsha): NAKAE SUSUMU 東京大学, 医科学研究所, 准教授 (60450409) ; MATSUMOTO KENJI 国立研究開発法人国立成育医療研究センター研究所, 免疫アレルギー感染研究部, 部長 (60181765) ; SUDO KATSUKO 東京医科大学, 医学部, 講師 (50126091)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: キチン / Ｔｈ２ / アレルギー / Th2

Outline of Final Research Achievements

Chitin, b-(1-4)-poly-N-acetyl-D-glucosamine, is a major constituent of the exoskeleton of house dust mite (HDM), raising the possibility that it may be involved in the development of HDM-related allergic disorders. However, the role of chitin in the pathogenesis of allergic disorders is poorly understood. Chitin enhances Th2-type immune responses in airway such as eosinophilia, IgE production and Th2-cytokine production dependently on the IL-33 production and IL-4/IL-13-STAT-6 pathway, resulting in aggravated OVA-induced airway inflammation in mice. Chitin-mediated IL-33 activates pulmonary DCs to induce excessive IL-1b production, and then the DCs enhance the activation of Th2 cells dependently on antigen and IL-1 signaling.

Research Products

• [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: In Press Issue: 5 Pages: 1395-1403
  • DOI: 10.1016/j.jaci.2016.01.032
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation by Promoting Regulatory T Cell Numbers. (2015)
  • Author(s): Morita H, Arae K, Unno H, Miyauchi K, Toyama S, Nambu A, Oboki K, Ohno T, Motomura K, Matsuda A, Yamaguchi S, Narushima S, Kajiwara N, Iikura M, Suto H, McKenzie AN, Takahashi T, Karasuyama H, Okumura K, Azuma M, Moro K, Akdis CA, Galli SJ, Koyasu S, Kubo M, Sudo K, Saito H, Matsumoto K, Nakae S.
  • Journal Title: Immunity Volume: 43 Issue: 1 Pages: 175-86
  • DOI: 10.1016/j.immuni.2015.06.021
  • NAID: 40020962854
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] IL-25 and IL-33 Contribute to Development of Eosinophilic Airway Inflammation in Epicutaneously Antigen-Sensitized Mice. (2015)
  • Author(s): Morita H, Arae K, Unno H, Toyama S, Motomura K, Matsuda A, Suto H, Okumura K, Sudo K, Takahashi T, Saito H, Matsumoto K, Nakae S.
  • Journal Title: PLoS One. Volume: 10 Issue: 7 Pages: e0134226-e0134226
  • DOI: 10.1371/journal.pone.0134226
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Silica and Double-Stranded RNA Synergistically Induce Bronchial Epithelial Apoptosis and Airway Inflammation (2014)
  • Author(s): Unno H, Futamura K, Morita H, Kojima R, Arae K, Nakae S, Ida H, Saito H, Matsumoto K, Matsuda A
  • Journal Title: Am J Respir Cell Mol Biol Volume: (in press) Issue: 3 Pages: 344-353
  • DOI: 10.1165/rcmb.2013-0281oc
  • Peer Reviewed
• [Journal Article] Role of IL-17A and IL-10 in the antigen induced inflammation model by Mycoplasma pneumoniae. (2014)
  • Author(s): Kurata S, Osaki T, Yonezawa H, Arae K, Taguchi H, Kamiya S
  • Journal Title: BMC Microbiology Volume: 14 Issue: 1 Pages: 156-156
  • DOI: 10.1186/1471-2180-14-156
  • Peer Reviewed / Open Access / Acknowledgement Compliant