Title of Presentation
“The Biochemical Dialogue Between Major Physiological Systems Mediated by Immune Cells”
The evolving field of immunoregulation studies how the activity of lymphocytes is shaped by their local environment via a variety of receptor interactions with soluble and cell-bound proteins. However, small metabolites derived from metabolism of immune cells are likely present in both intracellular and extracellular milieu in vivo, many of which may have signaling potential we have yet to understand. A growing body of research addresses the flux in metabolic products produced and consumed by different immune cells in various stages of differentiation and activation. We hypothesized that water-soluble metabolites provide environmental cues which mediate interactions between immune cells and thereby regulate their functions. I will discuss how a small metabolite produced and secreted by B cells and plasma cells promotes monocyte differentiation into anti-inflammatory macrophages which secrete IL-10 and inhibit CD8+ T cell killer function and anti-tumor responses. We propose that in addition to cytokines and membrane proteins, small metabolites derived from B lineage cells have immunoregulatory functions, which may be pharmaceutical targets allowing fine-tuning of immune responses.
Profile
- Web Site URL
- https://www.ccii.med.kyoto-u.ac.jp/en/member/
- https://www.ims.riken.jp/labo/12/cv.html
- A brief Biography(As of August 1 2021)
-
2000 Ph.D., Kyoto University 2000 Postdoctoral fellow, Department of Medical Chemistry, Faculty of Medicine, Kyoto University 2002 Team leader, Laboratory for Mucosal Immunity, RIKEN Center for Allergy and Immunology 2013-Present Team leader, Laboratory for Mucosal Immunity, RIKEN Center for Integrative Medical Sciences 2020-Present Professor, Division of Integrated High-Order Regulatory Systems, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University - Details of selected Awards and Honors
-
2005 Young Scientist Award from the Ministry of Education, Culture, Sport, Science and Technology, Japan 2012 Achievements Award from the Japanese Society for Immunology 2013 NISTEP Award from the Ministry of Education, Culture, Sport, Science and Technology, Japan 2020 1st Kobayashi Prize from Kobayashi Foundation - A list of selected Publications
-
Fagarasan S, Kinoshita K, Muramatsu M, Ikuta K, Honjo T. In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Nature. 2001 Oct 11;413(6856):639-43.PMID: 11675788
Fagarasan S, Muramatsu M, Suzuki K, Nagaoka H, Hiai H, Honjo T. Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora. Science. 2002 Nov 15;298(5597):1424-7.PMID: 12434060
Suzuki K, Meek B, Doi Y, Muramatsu M, Chiba T, Honjo T, Fagarasan S. Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut. Proc Natl Acad Sci USA. 2004 Feb 17;101(7):1981-6. PMID: 14766966
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. 2008, 29, 261-271. PMID: 18656387
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, 2009, 323, 1488-1492. PMID: 19286559
Suzuki K, Maruya M, Kawamoto S, Sitnik K., Kitamura H, Agace WW, Fagarasan S. The sensing of environmental stimuli by follicular dendritic cells promotes IgA generation in the gut. Immunity, 2010 Jul 23;33(1):71-83. PMID: 20727036
Kawamoto S, Tran TH, Maruya M, Suzuki K, Doi Y, Yumi T, Kato ML, Fagarasan S. The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut. Science 2012, 336(6080):485-9. PMID: 22539724
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. 2014 Jul 17;41(1):152-65. doi: 10.1016/j.immuni.2014.05.016.PMID: 25017466
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 and emotional behavior. Nat Immunol. 2017, Dec 18 (12):1342-1352
Nakajima A, Vogelzang A, Maruya M, Miyajima M, Murata M, Son A, Kuwahara T, Tsuruyama T, Yamada S, Matsuura M, Nakase H, Peterson DA, Fagarasan S, Suzuki K. IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria. J Exp Med. 2018 Aug 6;215(8):2019-2034. doi: 10.1084/jem.20180427. PMID:30042191
