RIKEN Center for Integrative Medical Sciences Laboratory for Mucosal Immunity

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

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Research Summary

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 Fields

Biology

Related Research Fields

Medicine, Dentistry & Pharmacy

Keywords

immunoglobulin A
gut microbiota
symbiosis
body homeostasis
Immunometabolism

Selected Publications

1. 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).
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."
Nature599, 471-476 (2021)
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)
4. 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)
5. 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)
6. 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).
7. 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)
8. Tsuji M, Komatsu N, Kawamoto S, Suzuki K, Kanagawa O, Honjo T, Hori S, Fagarasan S.
"Preferential generation of follicular B helper T (T_FH) 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).