Elucidation of the roles of regulatory T cells in symbiosis with commensal bacteria

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590563
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: NISHIO Junko 東京大学, 生産技術研究所, 特任助教 (40598679)
• Project Period (FY): 2011 – 2013
• Keywords: 腸管粘膜 / 制御性T細胞 / 免疫寛容 / Helios

Research Abstract

Immune system, which has been evolved to exclude pathogens, also has various mechanisms of avoidance of reaction to self tissue, which is called self-tolerance. Although intestinal immune cells continuously stimulated by intestinal commensal microbiota (CM), strong immune response to eradicate CM never occurs, suggesting intestinal mucosa bear very specific mechanisms of immune tolerance to CM.
Regulatory T cells (Tregs), which play a critical role in maintenance of self-tolerance by regulating immune cell activation, are known to be accumulated in the intestinal mucosa. However, it has been remained unclear how these cells are significant and are differentiated in steady state intestinal mucosa. By using a mouse model mouse bearing limited repertoire of TCR, we demonstrated that CB-derived antigens are important for differentiation of Tregs in the intestin and these Tregs contribute to intestinal homeostasis via suppressing DC activation which results in effector T cell activation.

Research Products

• [Journal Article] Differential Response of Regulatory and Conventional CD4+ Lymphocytes to CD3 Engagement : Clues to a Possible Mechanism of Anti-CD3 Action? (2013)
  • Author(s): Li L, Nishio J, van Maurik A, Mathis D, Benoist C
  • Journal Title: J Immunol Volume: 191(7) Pages: 3694 -704
  • Peer Reviewed
• [Journal Article] Conditional ablation of HMGB1 in mice reveals its protective function against endotoxemia and bacterial infection (2013)
  • Author(s): Yanai H, Matsuda A, An J, Koshiba R, Nishio J, Negishi H, Ikushima H, Onoe T, Ohdan H, Yoshida N, Taniguchi T
  • Journal Title: Proc. Natl. Acad. Sci. U S A Volume: 110(51) Pages: 20699-704
  • Peer Reviewed
• [Journal Article] Immunoregulation by the gut microbiota (2012)
  • Author(s): Nishio J, Honda K
  • Journal Title: Cell Mol Life Sci Volume: 69(21) Pages: 3635-50
  • Peer Reviewed
• [Journal Article] Essential contribution of IRF3 to intestinal homeostasis and microbiota-mediated Tslp gene induction (2012)
  • Author(s): Negishi H, Miki S, Sarashina H, Taguchi-Atarashi N, Nakajima A, Matsuki K, Endo N, Yanai H, Nishio J, Honda K and Taniguchi T
  • Journal Title: Proc Natl Acad Sci U S A Volume: 18;109(51) Pages: 21016-21021
  • Peer Reviewed
• [Journal Article] Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses (2012)
  • Author(s): Negishi H, Yanai H, Nakajima A, Koshiba R, Atarashi K, Matsuda A, Matsuki K, Miki S, Doi T, Aderem A, Nishio J, Smale ST, Honda K, Taniguchi T
  • Journal Title: Nat Immunol Volume: 13(7) Pages: 659-666
  • Peer Reviewed
• [Journal Article] 抗CD3抗体などによる自己免疫疾患の制御
  • Author(s): 西尾純子
  • Journal Title: 細胞工学 Volume: (掲載決定)
• [Presentation] Impact of TCR repertoire on intestinal homeostasis (2013)
  • Author(s): 西尾純子
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉県、幕張メッセ
  • Year and Date: 2013-12-13
• [Presentation] Imapact of TCR repertoire on Intestinal Homeostasis (2013)
  • Author(s): Junko Nishio
  • Organizer: The Gut Microbiome : The Effetor/Regulatory Immune Network
  • Place of Presentation: Taos, New Mexico, USA
  • Year and Date: 2013-10-15
• [Book] 新しい乳酸菌の機能と応用, 腸管の恒常性維持や免疫機構における腸内細菌の役割 (2013)
  • Author(s): 西尾純子
  • Total Pages: 17-27
  • Publisher: シーエムシー出版