Research and Education

Homeostasis can be defined as the ability of each tissue of the body to adapt its function to the environmental stimuli in a time and space specific manner, aimed to the optimal performance of the tissue and the overall fitness of the organism. Fine-tuned regulation of the immune function is critical for homeostasis of the immune system and interacting systems like the gastrointestinal tract and its microbiome, cardiovascular, and central nervous system. Indeed, in inflammatory settings, we revealed that the strong metabolic needs of the immune system can have an impact on the systemic availability of essential cell building blocks such as amino acids, affecting distant physiological process such as neurotransmitter synthesis in the brain.
Our laboratory aims to clarify how immune system co-opts such metabolites and neurotransmitters together with their downstream signaling for proper homeostasis. The global map of networking among different regulatory systems will provide new insights to overcome the gap between these machineries and establishing new categories of strategy to cure immune-related diseases.

B cell-derived GABA elicits IL-10+macrophages to limit anti-tumour immunity

Laboratory members

Recet Publications

1. Muna Al-Habsi, Kenji Chamoto, Ken Matsumoto, Norimichi Nomura, Baihao Zhang, Yuki Sugiura, Kazuhiro Sonomura, Aprilia Maharani, Yuka Nakajima, Yibo Wu, Yayoi Nomura, Rosemary Menzies, Masaki Tajima, Koji Kitaoka, Yasuharu Haku, Sara Delghandi, Keiko Yurimoto, Fumihiko Matsuda, So Iwata, Toshihiko Ogura, Sidonia Fagarasan, Tasuku Honjo. Spermidine activates mitochondrial trifunctional protein & improves antitumor immunity in mice, Science 378(6618) eabj3510 Oct 28, (2022). DOI: https://www.science.org/doi/10.1126/science.abj3510
2. 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. Nature 599, 471-476 (2021). DOI: https://doi.org/10.1038/s41586-021-04082-1
3. 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). DOI: https://www.nature.com/articles/ni.3867
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 & facilitate diversification of bacterial species responsible for immune homeostasis. Immunity. 2014 Jul 17;41(1):152-65. DOI: 10.1016/j.immuni.2014.05.016
5. Kawamoto, S., Tran, TH., Maruya, M., Suzuki, K., Doi, Y., Yumi, T., Kato, ML., Fagarasan, S. The inhibitory receptor PD-1 regulates IgA selection & bacterial composition in the gut. Science 2012, 336(6080):485-9. DOI: 10.1126/science.1217718

Laboratory

Professor: Sidonia FAGARASAN
Junior Associate Professor: Masaki TAJIMA
Assistant Professor: Akihiro SHIMBA

URL: https://www.ccii.med.kyoto-u.ac.jp/en/research/divisions-labs/division-of-integrated-high-order-regulatory-systems/