Regulation of autoimmunity by self-reactive regulatory T cells

2011 Fiscal Year Final Research Report

• Project Area: Immunological Self Recognition and its Disorders
• Project/Area Number: 19059014
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: HORI Shogei 独立行政法人理化学研究所, 免疫恒常性研究ユニット, ユニットリーダー (50392113)
• Project Period (FY): 2007 – 2011
• Keywords: 自己免疫 / 免疫寛容 / 自己反応性 / T細胞レセプター / 抗原特異性 / 制御性T細胞 / 細胞分化

Research Abstract

Foxp3^+ regulatory T (Treg) cells play a key role in establishing and maintaining natural self-tolerance. We have established a novel method for high-throughput analysis of the T cell receptor (TCR) repertoire using the next generation sequencing technology. By applying this method, we have analyzed the TCR repertoires of Foxp3^+ and Foxp3^- T cells and found that they are largely distinct. While this dissimilarity was established within the thymus, the repertoire of Foxp3^+ T cells was reshaped substantially in the periphery. In addition, we have also found that the normal T cell repertoire harbored a population of Foxp3- helper T cells with previous history of Foxp3 expression and that their TCR repertoire was distinct from Foxp3^+ Treg cells. Our results suggest that TCR specificity plays a central role in the lineage commitment of Treg cells.

Research Products

• [Journal Article] Plasticity of Foxp3^+ T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells (2012)
  • Author(s): Miyao T, Floess S, Setoguchi R, Luche H, Fehling HJ, Waldmann H, Huehn J, Hori S.
  • Journal Title: Immunity Volume: 36 Pages: 265-275
  • Peer Reviewed
• [Journal Article] Stability of regulatory T-cell lineage (2011)
  • Author(s): Hori S.
  • Journal Title: Advances in Immunology Volume: 112 Pages: 1-24
  • Peer Reviewed
• [Journal Article] Sustained suppression by Foxp3^+ regulatory T cells is vital for infectious transplantation tolerance (2011)
  • Author(s): Kendal AR, Chen Y, Regateiro FS, Ma J, Adams E, Cobbold SP, Hori S, Waldmann H.
  • Journal Title: Journal of Experimental Medicine Volume: 208 Pages: 2043-2053
  • Peer Reviewed
• [Journal Article] Regulatory T cell plasticity: beyond the controversies (2011)
  • Author(s): Hori S.
  • Journal Title: Trends in Immunology Volume: 32 Pages: 295-300
  • Peer Reviewed
• [Journal Article] Induction of colonic regulatory T cells by indigenous Clostridium species (2011)
  • Author(s): Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, Taniguchi T, Takeda K, Hori S, Ivanov II, Umesaki Y, Itoh K, Honda K.
  • Journal Title: Science Volume: 331 Pages: 337-341
  • Peer Reviewed
• [Journal Article] Developmental plasticity of Foxp3 Developmental plasticity of Foxp3^+ regulatory T cells (2010)
  • Author(s): Hori S.
  • Journal Title: Current Opinion in Immunology Volume: 22 Pages: 575-582
  • Peer Reviewed
• [Journal Article] Activated regulatory T cells are the major T cell type emigrating from sensitized skin (2010)
  • Author(s): Tomura M, Honda T, Tanizaki H, Otsuka A, Egawa G, Tokura Y, Waldmann H, Hori S, Cyster JG, Watanabe T, Miyachi Y, Kanagawa O, Kabashima K.
  • Journal Title: Journal of Clinical Investigation Volume: 120 Pages: 883-893
  • Peer Reviewed
• [Journal Article] Preferential generation of follicular B helper T (T_<FH> cells from Foxp3^+ T cells in gut Peyer’s patches (2009)
  • Author(s): Tsuji M, Komatsu N, Kawamoto S, Kanagawa O, Honjo T, Hori S, Fagarasan S.
  • Journal Title: Science Volume: 323 Pages: 1488-1492
  • Peer Reviewed
• [Journal Article] Heterogeneity of natural Foxp3^+ T cells a committed regulatory T cell lineage and an uncommitted minor population retaining plasticity (2009)
  • Author(s): Komatsu N, Mariotti-Ferrandiz ME, Wang Y, Malissen B, Waldmann H, Hori S.
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 106 Pages: 1903-1908
  • Peer Reviewed
• [Journal Article] Rethinking the molecular definition of regulatory T cells (2008)
  • Author(s): Hori S.
  • Journal Title: European Journal of Immunology Volume: 38 Pages: 928-930
  • Peer Reviewed
• [Presentation] T cell Differentiation and Plasticity (2012)
  • Author(s): Hori S.
  • Organizer: Resolving the controversy over regulatory T cell plasticity. The 14^<th> International Conference on Lymphocyte Activation and Immune Regulation
  • Place of Presentation: Newport Beach, CA, USA
  • Year and Date: 20120203-05
• [Presentation] Stability and plasticity in regulatory T cell differentiation. Keystone Symposia (2010)
  • Author(s): Hori S.
  • Organizer: Tolerance and Autoimmunity
  • Place of Presentation: Taos, New Mexico, USA
  • Year and Date: 20100221-26
• [Presentation] Foxp3 and its essential function for T cell regulation, International Symposium (2008)
  • Author(s): Hori S.
  • Organizer: Frontiers in Allergy and Autoimmunity
  • Place of Presentation: Mainz, Germany
  • Year and Date: 20080530-31
• [Presentation] Molecular mechanisms of dominant tolerance: lessons learned from naturally occurring Foxp3 gene mutations (2007)
  • Author(s): Hori S.
  • Organizer: The 13^<th> International Congress of Immunology
  • Place of Presentation: Rio de Janeiro, Brazil
  • Year and Date: 20070821-25
• [Remarks]
  • URL: http://www.riken.jp/r-world/research/lab/rcai/home/index.html