Role of chitinases in development of allergic asthma.

• Project/Area Number: 18K08395
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Kyorin University
• Principal Investigator: Arae Ken 杏林大学, 保健学部, 准教授 (50306669)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: キチン / アレルギー / Th2

Outline of Final Research Achievements

Exposure to various antigens derived from house dust mites (HDM) is considered to be a risk factor for development of certain allergic diseases such as atopic asthma. Chitin is an insoluble polysaccharide and a major component in the outer shell of HDMs. Mice exposed to chitin develop asthma-like airway eosinophilia. In the present study, we show that chitin induced production of IL-33 and TSLP by alveolar and bronchial epithelial cells, respectively, in mice. IL-25, IL-33 and TSLP were reported to be important for group 2 innate lymphoid cell (ILC2)-, but not Th2 cell-, dependent airway eosinophilia in a certain model using chitin beads. Here, we show that epithelial cell-derived IL-33 and TSLP, but not IL-25, were crucial for activation of resident lung Th2 cells as well as ILC2s to produce IL-5, resulting in development of chitin-induced airway eosinophilia.

Academic Significance and Societal Importance of the Research Achievements

キチンは、寄生虫のほか、エビ・カニなどの甲殻類、ハチ・ゴキブリなどの昆虫類、カビなどの真菌類に共通する外殻構成成分となっている。興味深いことに、これらの生物はヒトにとってアレルギー応答・2型免疫応答（Th2細胞、好酸球およびIgE産生を中心とする免疫応答）を引き起こす生物群である。したがって、キチンによる炎症誘発機構を解明できれば、アレルギー疾患のみならず、寄生虫の感染防御機構の解明に大きな貢献をもたらす可能性も期待される。

Research Products

• [Journal Article] Interleukin-33 and thymic stromal lymphopoietin, but not interleukin-25, are crucial for development of airway eosinophilia induced by chitin (2021)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Critical role of IL-33, but not IL-25 or TSLP, in silica crystal-mediated exacerbation of allergic airway eosinophilia (2020)
  • Author(s): Unno Hirotoshi、Arae Ken、Matsuda Akira、Ikutani Masashi、Tamari Masato、Motomura Kenichiro、Toyama Sumika、Suto Hajime、Okumura Ko、Matsuda Akio、Morita Hideaki、Sudo Katsuko、Saito Hirohisa、Matsumoto Kenji、Nakae Susumu
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 533 Issue: 3 Pages: 493-500
  • DOI: 10.1016/j.bbrc.2020.09.046
  • Peer Reviewed / Open Access
• [Journal Article] Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid (2019)
  • Author(s): Morita H, Kubo T, Ruckert B, Ravindran A, Soyka M, Rinaldi A, Sugita K, Wawrzyniak M, Wawrzyniak P, Motomura K, Tamari M, Orimo K, Okada N, Arae K, Saito K, Altunbulakli C, Castro-Giner F, Tan G, Neumann A, Sudo K, O’Mahony L, Honda K, Nakae S, Saito H, Mjösberg J, Nilsson G, Matsumoto K, Akdis M, Akdis CA
  • Journal Title: J Allergy Clin Immunol. Volume: in press Issue: 6 Pages: 2190-2201
  • DOI: 10.1016/j.jaci.2018.12.1018
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] IL-33, IL-25 and TSLP contribute to development of fungal-associated protease-induced innate-type airway inflammation (2018)
  • Author(s): Hiraishi Yoshihisa、Yamaguchi Sachiko、Yoshizaki Takamichi、Nambu Aya、Shimura Eri、Takamori Ayako、Narushima Seiko、Nakanishi Wakako、Asada Yosuke、Numata Takafumi、Suzukawa Maho、Yamauchi Yasuhiro、Matsuda Akira、Arae Ken、Morita Hideaki、Hoshino Tomoaki、Suto Hajime、Okumura Ko、Matsumoto Kenji、Nakae Susumu
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 18052-18052
  • DOI: 10.1038/s41598-018-36440-x
  • Peer Reviewed / Open Access
• [Journal Article] The roles of IL-17C in T cell-dependent and -independent inflammatory diseases (2018)
  • Author(s): Yamaguchi Sachiko、Nambu Aya、Numata Takafumi、Yoshizaki Takamichi、Narushima Seiko、Shimura Eri、Hiraishi Yoshihisa、Arae Ken、Morita Hideaki、Matsumoto Kenji、Hisatome Ichiro、Sudo Katsuko、Nakae Susumu
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 15750-15750
  • DOI: 10.1038/s41598-018-34054-x
  • Peer Reviewed / Open Access
• [Journal Article] Gastrin-Releasing Peptide Is Involved in the Establishment of Allergic Rhinitis in Mice (2018)
  • Author(s): Matsumoto Yuma、Yokoi Hidenori、Kimura Toru、Matsumoto Yoshifumi、Kawada Michitsugu、Arae Ken、Nakae Susumu、Ikeda Tetsuya、Matsumoto Kenji、Sakurai Hiroyuki、Saito Koichiro
  • Journal Title: The Laryngoscope Volume: 128 Issue: 11
  • DOI: 10.1002/lary.27394
  • Peer Reviewed
• [Journal Article] Chitin promotes antigen-specific Th2 cell-mediated murine asthma through induction of IL-33-mediated IL-1β production by DCs (2018)
  • Author(s): Arae Ken、Morita Hideaki、Unno Hirotoshi、Motomura Kenichiro、Toyama Sumika、Okada Naoko、Ohno Tatsukuni、Tamari Masato、Orimo Keisuke、Mishima Yuko、Suto Hajime、Okumura Ko、Sudo Katsuko、Miyazawa Hiroshi、Taguchi Haruhiko、Saito Hirohisa、Matsumoto Kenji、Nakae Susumu
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 11721-11721
  • DOI: 10.1038/s41598-018-30259-2
  • Peer Reviewed / Open Access
• [Journal Article] IL-31 is crucial for induction of pruritus, but not inflammation, in contact hypersensitivity (2018)
  • Author(s): Takamori Ayako、Nambu Aya、Sato Keiko、Yamaguchi Sachiko、Matsuda Kenshiro、Numata Takafumi、Sugawara Takeru、Yoshizaki Takamichi、Arae Ken、Morita Hideaki、Matsumoto Kenji、Sudo Katsuko、Okumura Ko、Kitaura Jiro、Matsuda Hiroshi、Nakae Susumu
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 6639-6639
  • DOI: 10.1038/s41598-018-25094-4
  • Peer Reviewed / Open Access
• [Journal Article] Isolation and characterisation of CD9-positive pituitary adult stem/progenitor cells in rats (2018)
  • Author(s): Horiguchi Kotaro、Fujiwara Ken、Yoshida Saishu、Nakakura Takashi、Arae Ken、Tsukada Takehiro、Hasegawa Rumi、Takigami Shu、Ohsako Shunji、Yashiro Takashi、Kato Takako、Kato Yukio
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1-15
  • DOI: 10.1038/s41598-018-23923-0
  • Peer Reviewed / Open Access
• [Journal Article] IL-25 enhances Th17 cell-mediated contact dermatitis by promoting IL-1b production by dermal dendritic cells (2018)
  • Author(s): Suto H, Nambu A, Morita H, Yamaguchi S, Numata T, Yoshizaki T, Shimura E, Arae K, Asada Y, Motomura K, Kaneko M, Abe T, Matsuda A, Iwakura Y, Okumura K, Saito H, Matsumoto K, Sudo K, Nakae S
  • Journal Title: J Allergy Clin Immunol Volume: In press Issue: 5 Pages: 1500-1509
  • DOI: 10.1016/j.jaci.2017.12.1007
  • Peer Reviewed / Open Access
• [Journal Article] The optimal age for epicutaneous sensitization following tape-stripping in BALB/c mice (2018)
  • Author(s): Tamari M, Orimo K, Motomura K, Arae K, Matsuda A, Nakae S, Saito H, Morita H, Matsumoto K
  • Journal Title: Allergology International Volume: 67 Issue: 3 Pages: 380-387
  • DOI: 10.1016/j.alit.2018.01.003
  • NAID: 130007420809
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access