Regulation of type 2 innate lymphoid cells by microbiota

• Project/Area Number: 18K16167
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Morita Hideaki 国立研究開発法人国立成育医療研究センター, 免疫アレルギー・感染研究部, 室長 (90365320)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 微生物叢 / アレルギー / 自然リンパ球 / 気管支喘息 / 2型自然リンパ球

Outline of Final Research Achievements

Allergic diseases, including asthma, are chronic inflammatory diseases that affect more than 200 million people all over the world. Therefore, it is critical to devise strategies for preventing allergic diseases. Recent findings suggest that gut microbiota and its metabolite affect systemic inflammatory diseases. In the present study, we attempt to clarify the roles of microbiota metabolite, especially short-chain fatty acid, in the regulation of group 2 innate lymphoid cells, one of the primary effector cells in allergic inflammation. As a result, we found that butyrate and propionate, but not acetate, suppress the activation of group 2 innate lymphoid cells. These findings may lead to the development of the strategy for the prevention of allergic diseases.

Academic Significance and Societal Importance of the Research Achievements

本研究により、腸内細菌が産生する物質である短鎖脂肪酸の一部が、アレルギー性の炎症誘導に深く関与する免疫細胞の活性を抑制することが明らかとなった。これらの事実から、この短鎖脂肪酸自体、もしくはこれらを誘導する細菌に着目することで、気管支喘息を含むアレルギー疾患の発症予防法の開発につながる可能性が示唆された。

Research Products

• [Int'l Joint Research] SIAF, University of Zurich(スイス)
• [Journal Article] Innate lymphoid cells in the airways: Their functions and regulators. (2020)
  • Author(s): Orimo K, Saito H, Matsumoto K, Morita H.
  • Journal Title: Allergy Asthma Immunol Res. Volume: 12 Issue: 3 Pages: 381-398
  • DOI: 10.4168/aair.2020.12.3.381
  • Peer Reviewed / Open Access
• [Journal Article] Human type 2 innate lymphoid cells disrupt skin keratinocyte tight junction barrier by IL-13 (2019)
  • Author(s): Sugita K, Altunbulakli C, Morita H, Sugita A, Kubo T, Kimura R, Goto H, Yamamoto O, Rückert B, Akdis M, Akdis CA.
  • Journal Title: Allergy Volume: 74 Issue: 12 Pages: 2534-2537
  • DOI: 10.1111/all.13935
  • Peer Reviewed / Int'l Joint Research
• [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] Gene expression signatures of circulating human type 1, 2 and 3 innate lymphoid cells. (2019)
  • Author(s): Li S, Morita H, Sokolowska M, Tan G, Boonpiyathad T, Opitz L, Orimo K, Archer SK, Jansen K, Tang MLK, Purcell D, Plebanski M, Akdis CA.
  • Journal Title: J Allergy Clin Immunol Volume: 143 Issue: 6 Pages: 2321-2325
  • DOI: 10.1016/j.jaci.2019.01.047
  • Peer Reviewed / Int'l Joint Research
• [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
• [Presentation] Role of innate immunity in the development of allergic diseases (2019)
  • Author(s): 1)Morita H, Matsumoto K
  • Organizer: The 48th Annual Meeting of the Japanese Society of Immunology
  • Invited
• [Presentation] Retinoic acid converts human group 2 innate lymphoid cells to a regulatory phenotype (2018)
  • Author(s): Morita H, Kubo T, Nakae S, Saito H, Matsumoto K, Akdis M, Akdis CA
  • Organizer: The 3rd International Conference on Innate Lymphoid Cells
  • Int'l Joint Research
• [Presentation] Innate immunity in allergic inflammation. (2018)
  • Author(s): Morita H
  • Organizer: The 14th Research Symposium on Human Natural Defense System
  • Int'l Joint Research / Invited
• [Presentation] Retinoic acid controls lung homeostasis by converting group 2 innate lymphoid cells to a regulatory phenotype (2018)
  • Author(s): Morita H
  • Organizer: 32nd Symposium of the Collegium Internationale Allergologium
  • Int'l Joint Research
• [Presentation] 好酸球性気道炎症の病態形成におけるILC2の役割 (2018)
  • Author(s): 森田英明
  • Organizer: 第67回日本アレルギー学会学術大会