Fagarasan Sidonia
moonshot_isa_master
氏名Name
Fagarasan Sidonia
所属・職名Affiliation, Title, etc.
Team Director, Laboratory for Mucosal Immunity, RIKEN Center for Integrative Medical Sciences
Professor, Division of Integrated High-Order Regulatory Systems, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University.
研究室HPWebsite
一言メッセージShort Message
Elucidating the brain's reservoir function mediated by serotonin through the gut-brain axis
本プロジェクトでの研究概要Outline of the research in this project
A neurotransmitter, serotonin is synthesized primarily from the brain and the gut and is known to contribute to inflammatory responses subsequent to tissue injury. Our research focus on the functions of serotonin beyond its role as a neurotransmitter, investigating how the reservoir function of brain is mediated by the gut-brain axis. We will comprehensively analyze serotonin levels and their impact in the brain and gut of mice raised under specific pathogen-free (SPF) and germ-free (GF) conditions using metabolomics, chemistry assays, and proteomics. In addition, using mouse models for neurodegenerative diseases, we will examine immune-related cells (e.g., microglia) to uncover target molecules for serotonin that are either gut microbiota-dependent or independent. To do this, we will utilize genetically knockout mice that lack either serotonin transporters or relevant enzymes to assess the role of serotonin in cognition, injury response, and the brain’s reservoir function.
これまで主な研究内容Outline of main research so far
The majority of our research has focused on the communication between immune cells and their regulatory impact on the host mouse microbiota, as well as how gut microbiota influence physiological aspects such as brain function, behavior, and susceptibility to diseases. In recent years, through the application of systems biology approaches, we have uncovered extensive microbial-immune interactions that reach beyond the gut and impact distant organs. We demonstrated that neurotransmitters in the brain mediate the effects of chronic systemic immune activation on behavior. Our more recent research revealed that γ-aminobutyric acid (GABA), a well-characterized neurotransmitter, is also a secreted immune metabolic product of B cells and IgA plasma cells. Moreover, inhibiting GABA function enhances antitumor immunity. Through this work, we introduced the concept of Secreted Immune Metabolites (SIMets), a new class of bioactive small molecular compounds secreted by immune cells. Our ongoing research aims to contextualize the effects of SIMets on antitumor immune responses, aging, and brain function, ultimately advancing our understanding of the immune system’s role in various biological and pathological processes.
主な経歴・受賞歴等Career, Awards, etc.
Academic & Research Experience
- 2020-present:
- Professor, Division of Integrated High-Order Regulatory Systems, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
- 2013-present:
- Team Director/Team leader, Laboratory for Mucosal Immunity, RIKEN Center for Integrative Medical Sciences (IMS) Yokohama, Japan
- 2002-2012:
- Team leader, Laboratory for Mucosal Immunity, RIKEN Center for Allergy and Immunology (RCAI)
Honors & Awards
- 2020:
- 1st Kobayashi Prize
- 2013:
- NISTEP Award from the Ministry of Education, Culture, Sport, Science and Technology, Japan.
- 2012:
- The 15th Japanese Society for Immunology (JSI) Award.
- 2005:
- Young Scientist Award from the Ministry of Education, Culture, Sport, Science and Technology, Japan.
主要業績Major Publications
Al-Habsi M, Chamoto K, Matsumoto K, Nomura N, Zhang B, Sugiura Y, Sonomura K, Maharani A, Nakajima Y, Wu Y, Nomura Y, Menzies R, Tajima M, Kitaoka K, Haku Y, Delghandi S, Yurimoto K, Matsuda F, Iwata S, Ogura T, Fagarasan S, Honjo T. Spermidine activates mitochondrial trifunctional protein & improves antitumor immunity in mice. Science, 378(6618), Oct 28, (2022).
https://doi.org/10.1126/science.abj3510
Zhang B, Vogelzang A, Miyajima M, Sugiura Y, Wu Y, Chamoto K, Nakano R, Hatae R, Menzies R.J, Sonomura K, Hojo N, Ogawa T, Kobayashi W, Tsutsui Y, Yamamoto S, Maruya M, Narushima S, Suzuki K, Sugiya H, Murakami K, Hashimoto M, Ueno H, Kobayashi T, Ito K, Hirano T, Shiroguchi K, Matsuda F, Suematsu M, Honjo T, Fagarasan S. Bcell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity. Nature599, 471-476 (2021)
https://doi.org/10.1038/s41586-021-04082-1
Miyajima, M, Zhang, B, Sugiura, Y, Sonomura, K, Guerrini, M.M, Tsutsui, Y, Maruya, M, Vogelzang, A, Chamoto, K, Honda, K, Hikida, T, Qin, H, Sanuki, R, Suzuki, K, Furukawa, T, Ishihama, Y, Matsuda, F, Suematsu, M, Honjo, T, Fagarasan, S. Metabolic shift induced by systemic activation of T cells in PD-1 deficient mice perturbs brain monoamines &emotional behavior. Nat Immunol. 18, 1342-1352 (2017)
https://doi.org/10.1038/ni.3867
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)
https://doi.org/10.1073/pnas.1608873113
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)
https://doi.org/10.1016/j.immuni.2014.05.016
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).
https://doi.org/10.1126/science.1217718
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)
https://doi.org/10.1016/j.immuni.2010.07.003
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).
https://doi.org/10.1126/science.1169152
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)
https://doi.org/10.1073/pnas.0307317101
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).
https://doi.org/10.1126/science.1077336
