Centers & Labs

RIKEN Center for Integrative Medical Sciences

Laboratory for Immune Homeostasis

Team Leader: Taishin Akiyama (Ph.D.)
Taishin  Akiyama(Ph.D.)

Disruption of immune systems can cause many types of diseases such as immunodeficiency, autoimmune diseases, allergy and tumor. Our team focuses on mechanisms establishing T cell self-tolerance in the thymus, which providing an environment for T cell differentiation. Several lines of evidence revealed critical roles of epithelial cells in the thymic medulla (medullary thymic epithelial cells; mTECs) for selecting self-tolerant T cells and regulatory T cells, thereby preventing onset of autoimmune diseases and controlling anti-tumor immunity. Our team aims to clarify mechanisms regulating function, differentiation, and maintenance of mTECs and to utilize the mTEC function for controlling immune-related diseases.

Main Research Field

Medicine, dentistry, and pharmacy

Related Research Fields

Biology

General medical chemistry / Immunology / Molecular biology

Keywords

  • Immune-related diseases
  • Autoimmunity
  • Lymphoid organs
  • T cells (T lymphocytes)
  • Thymic epithelial cells

Selected Publications

Papers with an asterisk(*) are based on research conducted outside of RIKEN.
  1. Horie K, Kudo T, Yoshinaga R, Akiyama N, Sasanuma H, Kobayashi TJ, Shimbo M, Jeon H, Miyao T, Miyauchi M, Shirakawa M, Shiba D, Yoshida N, Muratani M, Takahashi S, Akiyama T*.:
    "Long-term hindlimb unloading causes a preferential reduction of medullary thymic epithelial cells expressing autoimmune regulator (Aire)."
    Biochem. Biophys. Res. Commun. 501:745-750 (2018)
  2. Kanaya T, Sakakibara S, Jinnohara T, Hachisuka M, Tachibana N, Hidano S, Kobayashi T, Kimura S, Iwanaga T, Nakagawa T, Katsuno T, Kato N, Akiyama T, Sato T, Williams IR, Ohno H.:
    "Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling."
    J. Exp. Med. 215:501-519 (2018).
  3. *Akiyama N, Takizawa N, Miyauchi M, Yanai H, Tateishi R, Shinzawa M, Yoshinaga R, Kurihara M, Demizu Y, Yasuda H, Yagi S, Wu G, Matsumoto M, Sakamoto R, Yoshida N, Penninger JM., Kobayashi Y, Inoue J, and Akiyama T*.:
    "Identification of embryonic precursor cells that differentiate into thymic epithelial cells expressing autoimmune regulator"
    J. Exp. Med. 213: 1441-1458 (2016)
  4. *Tateishi R, Akiyama N, Miyauchi M, Yoshinaga R, Sasanuma H, Kudo T, Shimbo M, Shinohara M, Obata K, Inoue J, Shirakawa M, Shiba D, Asahara H, Yoshida N, Takahashi S, Morita H, and Akiyama T*.:
    "Hypergravity provokes a temporary reduction in CD4+CD8+ thymocyte number and a persistent decrease in medullary thymic epithelial cell frequency in mice."
    Plos one., 10: e0141650 (2015)
  5. *Varney M, Niederkorn M, Konno H, Matsumura T, Gohda J, Yoshida N, Akiyama T, Christie S, Fang J, Miller D, Jerez A, Karsan A, Maciejewski J, Meetei M, Inoue J, and Starczynowski D.:
    "Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor/TRAF6 signaling."
    J. Exp. Med. , 212: 1967-1985 (2015)
  6. *Shinzawa M., Konno H., Qin J., Akiyama N., Miyauchi M, Ohashi H., Miyamoto-Sato E., Yanagawa H., Akiyama T*, and Inoue J.:
    "Catalytic subunits of the phosphatase calcineurin interact with NF-κB-inducing kinase (NIK) and attenuate NIK-dependent gene expression."
    Sci. Rep., 5: 10758 (2015)
  7. *Akiyama N., Shinzawa M., Miyauchi M., Yanai H., Tateishi R., Shimo Y., Ohshima D., Matsuo K., Sasaki I., Hoshino K., Wu G., Yagi S. Inoue J., Kaisho T., and Akiyama T*.:
    "Limitation of immune tolerance–inducing thymic epithelial cell development by Spi-B–mediated negative feedback regulation."
    J. Exp. Med. , 211: 2425-2438 (2014)
  8. *Akiyama T*, Shimo Y, Yanai H, Qin J, Ohsima, D, Maruyama Y, Asaumi Y, Kitazawa J, Takayanagi H, Penninger JM, Matsumoto M, Nitta T, Takahama Y, and Inoue J.:
    "The Tumor necrosis family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance"
    Immunity, 29: 423-437 (2008).
  9. *Hikosaka Y, Nitta T, Ohigashi I, Yano K, Ishimaru N, Hayashi Y, Matsumoto M, Matsuo K, Penninger JM, Takayanagi H, Yokota Y, Yamada H, Yosikai Y, Inoue J, Akiyama T, and Takahama Y.:
    "The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator."
    Immunity, 29, 438-450 (2008)
  10. *Akiyama T, Maeda S, Yamane S, Ogino K, Kasai M, Kajiura F, Matsumoto M, and Inoue J.:
    "Dependence of Self-tolerance on TRAF6-directed Development of Thymic Stroma."
    Science, 308: 248-251 (2005)

Lab Members

Principal Investigator

Taishin Akiyama
Team Leader

Core Members

Takahisa Miyao
Technical Scientist
Takao Seki
Postdoctoral Researcher
Maki Miyauchi
Technical Staff I

Contact information

1-7-22 Suehiro-cho, Tsurumi-ku,
Yokohama City, Kanagawa,
230-0045, Japan
Tel: +81-(0)45-503-7069

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