MembersMembers and Laboratories

Division of Integrated High-Order Regulatory Systems

Our Research

Area of Research Covered in this Laboratory

Immune activation: Metabolic reprogramming of innate and adaptive immune cells associated with activation.
Immune regulation: Deciphering the new language between immune cells mediated by metabolites. Role of small metabolites as signaling molecules regulating the immune cell function. Targeting the metabolism pathways aiming at enhancing anti-cancer immunity or taming autoimmune responses.
Immune integration: Modes of communication between the immune system, microbiota and other major physiological systems. Impact of the immune cells on microbial and brain endocrinology in homeostasis and diseases.

Brief Description

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. For immune homeostasis, extracellular signals partner with intracellular biochemical pathways to orchestrate the immune response. Surface receptors, cytokines and hormones including neurotransmitters are all involved in regulation of the immune cell function. Cytokines and their receptors are necessary for feed-forward and feed-back regulations required for proper immune responses relating to self-tolerance and symbiosis with endogenous bacterial communities or targeting and eliminating pathogens or cancers. Metabolites and hormones including neurotransmitters-derived from immune cells, bacterial or neuronal metabolism, provide additional environmental cues likely mediating the immune cells function.
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 or central nervous system. Indeed, in inflammatory settings like autoimmunity or cancer immunotherapy, 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 at high resolution 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 establish new categories of strategy to cure immune-related diseases.

For your reference:


Sidonia Fagarasan, MD, PhD

Assistant Professor
Masaki Tajima, PhD

Muna Al-Habsi
Lin Yu-Hsien, PhD
He Hao, PhD

Demir Melike Fusun
Surabhi Raman

Technical Staff
Sayaka Washizu
Pedro Cruz, PhD

Midori Okabe

Visiting Researcher
Baihao Zhang, PhD

Collaborative Technical Staff
Mikako Maruya


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. B cell-derived GABA elicits IL-10⁺ macrophages to limit anti-tumour immunity. Nature. 2021 Nov 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 and emotional behavior. Nat Immunol. 2017, Dec 18 (12):1342-1352

Recruitment & Contact

We are recruiting highly motivated young scientists (graduate students and postdoctoral fellows) and technical staff regardless of previous scientific backgrounds.
Please contact us using the form linked below for recruitment and other inquiries.
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