Laboratory for Mucosal Immunity

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.

Research Fields

Biology & Biochemistry / Molecular Biology & Genetics / Immunology / Clinical Medicine / Microbiology

Research Subjects

• Contribution of microbiota to immune maturation, fitness and tolerance
• Impact of immune system on diversity, structure and resilience of gut microbiota
• An extended loop of activation; gut microbiota and systemic responses

Publications

1. 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).
2. Sutherland DB, Fagarasan S.:
   "IgA synthesis: a form of functional immune adaptation extending beyond gut."
   Curr Opin Immunol, 24: 261-268. (2012)
3. Wei M, Shinkura R, Doi Y, Maruya M, Fagarasan S, Honjo T.:
   "Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense."
   Nat. Immunol, 12:264-270. (2011)
4. Maruya M, Suzuki K, Fujimoto H, Miyajima M, Kanagawa O, Wakayama T, Fagarasan S.:
   "Vitamin A-dependent transcriptional activation of the nuclear factor of activated T cells c1 (NFATc1) is critical for the development and survival of B1 cells."
   Proc. Natl. Acad. Sci. U.S.A., 108:722-727. (2011)
5. 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)
6. 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)
7. 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).
8. Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K, Ivaylo II, Itoh K, Littman DR, Fagarasan S.:
   "Requirement for Lymphoid tissue inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut."
   Immunity 29:261-271 (2008).
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).