Centers & Labs

RIKEN Center for Integrative Medical Sciences

Laboratory for Mucosal Immunity

Team Leader: Sidonia Fagarasan (M.D., Ph.D)
Sidonia  Fagarasan(M.D., Ph.D)

The main function of the immune system is to protect the host against pathogens, such as bacteria or viruses. However, unlike the systemic immune system, the gut immune system does not eliminate microorganisms but instead nourishes rich bacterial communities and establishes advanced symbiotic relationships. We aim to understand the feed-forward and feedback mechanisms between microbiota and the immune system at the mucosal barrier. We intend to elucidate the contribution of each component of the immune system to the trademark characteristics of microbiota namely diversity, balance and metabolic functions. This knowledge seems particularly important for translational medicine, especially when considering strategies to correct the defects and to reestablish symbiosis in intestinal pathologies like infections, inflammatory diseases and malabsorbtion associated with various immuno-deficiencies -primary or secondary, single or combined.

Main Research Field

Biology

Related Research Fields

Medicine, dentistry, and pharmacy

Keywords

  • immunoglobulin A
  • gut microbiota
  • symbiosis
  • body homeostasis

Selected Publications

  1. Chamoto K, Chowdhury PS, Kumar A, Sonomura K, Matsuda F, Fagarasan S, Honjo T.
    "Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity."
    Proc Natl Acad Sci U S A. 114(5):E761-E770 (2017)
  2. Zhang B, Chikuma S, Hori S, Fagarasan S, Honjo T.
    "Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model."
    Proc Natl Acad Sci U S A, 113(30):8490-5 (2016)
  3. Sutherland DB, Suzuki K, Fagarasan S.
    "Fostering of advanced mutualism with gut microbiota by Immunoglobulin A."
    Immunol Rev., 270(1), 20-31 (2016)
  4. Kawamoto S, Maruya M, Kato LM, Suda W, Atarashi K, Doi Y, Tsutsui Y, Qin H, Honda K, Okada T, Hattori M, Fagarasan S.:
    "Foxp3(+) T cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis."
    Immunity, 41(1), 152-65 (2014)
  5. Kawamoto S, Tran TH, Maruya M, Suzuki K, Doi Y, Tsutsui Y, Kato LM, Fagarasan S.:
    "The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut."
    Science, 336(6080), 485-9 (2012).
  6. Suzuki K, Maruya M, Kawamoto S, Sitnik K, Kitamura H, Agace WW, Fagarasan S.:
    "The sensing of environmental stimuli by follicular dendritic cells promotes immunoglobulin A generation in the gut."
    Immunity, 33:71-83 (2010)
  7. Fagarasan S, Kawamoto S, Kanagawa O, Suzuki K.:
    "Adaptive immune regulation in the gut: T cell-dependent and T cell-independent IgA synthesis."
    Annu. Rev. Immunol. 28:243-273. (2010)
  8. Tsuji M, Komatsu N, Kawamoto S, Suzuki K, Kanagawa O, Honjo T, Hori S, Fagarasan S.
    "Preferential generation of follicular B helper T (TFH) cells from Foxp3+ T cells in gut Peyer's patches."
    Science, 323:1488-1492 (2009).
  9. Suzuki, K., Meek, B., Doi, Y., Muramatsu, M., Chiba, T., Honjo, T., and Fagarasan, S.:
    "Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut"
    Proc. Natl. Acad. Sci. USA, 101, 1981-1986 (2004)
  10. Fagarasan, S., Muramatsu, M., Suzuki, K., Nagaoka, H., Hiai, H., and Honjo, T.:
    "Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora"
    Science, Nov 15, 298 (5597), 1424-7 (2002).

Lab Members

Principal Investigator

Sidonia Fagarasan
Team Leader

Core Members

Keiichiro Suzuki
Senior Research Scientist
Michio Miyajima
Research Scientist
Matteo Guerrini
Research Scientist
Satomi Ito
Research Scientist
Alexis Vogelzang
Special Postdoctoral Researcher
Baihao Zhang
Postdoctoral Researcher
Mikako Maruya
Research Associate
Yumi Tsutsui
Technical Staff I
Wakana Kobayashi
Technical Staff II
Sachiko Yamamoto
Technical Staff II

Contact information

1-7-22 Suehiro-cho, Tsurumi-ku,
Yokohama City, Kanagawa,
230-0045, Japan
Tel: +81-(0)45-503-7029
Fax: +81-(0)45-503-7027

Email: sidonia.fagarasan [at] riken.jp

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