Molecular mechanisms for IgA-mediated regulations of host-microbiota symbiosis

• Project/Area Number: 16H02632
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Fagarasan Sidonia 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (00391970)
• Co-Investigator(Kenkyū-buntansha): 服部 正平 早稲田大学, 理工学術院, 教授(任期付) (70175537)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥43,810,000 (Direct Cost: ¥33,700,000、Indirect Cost: ¥10,110,000); Fiscal Year 2018: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000); Fiscal Year 2017: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000); Fiscal Year 2016: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
• Keywords: Immunology / IgA

Outline of Final Research Achievements

In this project we gained important insights into the characteristics and function of mucosal immunoglobulin A (IgAs). Furthermore, we identified and characterized IgA-dependent gene elements of Bacteroides species that are critical factors for regulation of mucosal homeostasis via the bacteria-bacteria interaction.

Academic Significance and Societal Importance of the Research Achievements

腸内細菌の乱れは炎症性腸疾患、自己免疫疾患、アレルギー性疾患、パーキンソン病を含む神経性疾患などの病態と大きく関わっている。本研究ではIgAによって腸内細菌にもたらされる遺伝子変化が炎症性腸疾患に対して防護的に働いている事が明らかとなった。今回の研究で同定された細菌遺伝子、あるいは腸管IgAの性質を制御する方法が明らかになれば、炎症性腸炎に対する新しい制御方法の開発につながる可能性がある。

Research Products

• [Journal Article] IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria. (2018)
  • Author(s): Nakajima A, Vogelzang A, Maruya M, Miyajima M, Murata M, Son A, Kuwahara T, Tsuruyama T, Yamada S, Matsuura M, Nakase H, Peterson DA, Fagarasan S, Suzuki K.
  • Journal Title: J Exp Med. Volume: 215 Issue: 8 Pages: 2019-2034
  • DOI: 10.1084/jem.20180427
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 1.Involvement of T cells in antibody diversification and shaping of the microbial landscape. (2018)
  • Author(s): Sidonia Fagarasan
  • Organizer: The Franco-Japanese seminar on Immunology
  • Int'l Joint Research / Invited
• [Presentation] Involvement of PD1 in antibody diversification and immune homeostasis (2016)
  • Author(s): Sidonia Fagarasan
  • Organizer: 第３２回（2016）京都賞記念ワークショップ 基礎科学部門
  • Place of Presentation: 京都大学百周年時計台記念館（京都市）
  • Year and Date: 2016-11-12
  • Int'l Joint Research / Invited
• [Presentation] Involvement of T cells in antibody diversification and shaping of the gut microbial landscape (2016)
  • Author(s): Sidonia Fagarasan
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: メルボルン
  • Year and Date: 2016-08-22
  • Int'l Joint Research / Invited