Immune Response Dynamics

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Immune regulation by the nervous system
It has long been proposed that various aspects of immune responses are influenced by nervous system activity. Indeed, lymphoid organs are innervated by various types of neurons, and immune cells express neurotransmitter receptors to respond to the neural inputs. However, little is known about how the inputs from the nervous system control immune responses. To solve this problem, we are studying the cellular and molecular basis for the neural regulation of immunity. Adrenergic nerves constitute the efferent arc of the sympathetic nervous system and produce noradrenaline that induces cellular responses through α1-, α2-, β1-, β2- and β3-adrenergic receptors. Like other vital organs, lymphoid organs, including the bone marrow, thymus, spleen and lymph nodes, receive a rich supply of adrenergic nerves. We found that inputs from adrenergic nerves control lymphocyte egress from lymph nodes through β2-adrenergic receptors (J. Exp. Med. 2014, Fig. 1). Additionally, our study demonstrated that this mechanism helps generate a diurnal rhythm of adaptive immune responses in lymph nodes (J. Exp. Med. 2016).

Developing novel therapeutic strategies for inflammatory diseases
Lymphocyte migration is mediated by G protein-coupled receptors (GPCRs) that respond to chemoattractants, represented by chemokines. In search of novel factors involved in chemoattractant receptor signaling, we identified a protein complex consisting of copper metabolism MURR1 domain-containing (COMMD) 3 and COMMD8 (COMMD3/8 complex) (J. Exp. Med. 2019). The COMMD3/8 complex interacts with the C-terminal tail of chemoattractant receptors and promotes lymphocyte chemotaxis mediated by the receptors (Fig. 2). Deficiency of the COMMD3/8 complex severely impaired B cell migration in vivo and humoral immune responses. Therefore, the COMMD3/8 complex is essential for proper functioning of the immune system. Our recent data suggest that the COMMD3/8 complex may be involved in the pathogenesis of inflammatory diseases. Pharmacological inhibition of the COMMD3/8 complex may provide a novel approach for the treatment of the immune disorders.

Control of lymphocyte trafficking by adrenergic nerves

Figure 1. Control of lymphocyte trafficking by adrenergic nerves
Activation of β2-adrenergic receptors expressed on lymphocytes enhances the responsiveness of CCR7 and CXCR4, chemokine receptors that promote lymph node retention of lymphocytes, and inhibits their egress from lymph nodes.

Role of the COMMD3/8 complex in chemoattractant receptor signaling

Figure 2. Role of the COMMD3/8 complex in chemoattractant receptor signaling
The COMMD3/8 complex functions as an adaptor that recruits GPCR kinase (GRK) 6 to chemoattractant receptors, promoting MAPK activation and consequently lymphocyte chemotaxis.

Principal Investigator

Kazuhiro Suzuki Professor

Research field: Neural regulation of adaptive immunity
Development of novel therapies for inflammatory diseases
Education history
2007.9 PhD, Graduate School of Medicine, Osaka University
2003.3 2003.3 MD, Medical School of Osaka University
1998.3 BSc, School of Science, The University of Tokyo
Research and career history
2017.7- Professor (concurrent), Research Institute for Microbial Diseases, Osaka University
2017.4- Professor, IFReC, Osaka University
2011.10-2015.3 PRESTO researcher, JST
2011.4-2017.3 Associate professor, IFReC, Osaka University
2007.10-2011.3 Postdoctoral fellow, University of California, San Francisco, USA
2006.4-2007.9 JSPS fellow (DC2)
2003.4-2004.3 Resident in internal medicine, Osaka University Hospital


Akiko Nakai Assistant Professor
Sarah Leach  Postdoctoral fellow
Yoshiko Ota Laboratory Technician
Yuka Miyoshi  Laboratory Technician


Nakai, A., Fujimoto, J., Miyata, H., Stumm, R., Narazaki, M., Schulz, S., Baba, Y., Kumanogoh, A. and Suzuki, K. The COMMD3/8 complex determines GRK6 specificity for chemoattractant receptors. J. Exp. Med. 216: 1630-1647, 2019.
Suzuki, K., Hayano, Y., Nakai, A., Furuta, F. and Noda, M. Adrenergic control of the adaptive immune response by diurnal lymphocyte recirculation through lymph nodes. J. Exp. Med. 213: 2567-2574, 2016.
Nakai, A., Hayano, Y., Furuta, F., Noda, M. and Suzuki, K. Control of lymphocyte egress from lymph nodes through β2-adrenergic receptors. J. Exp. Med. 211: 2583-2598, 2014.
Green, J.A., Suzuki, K., Cho, B., Willison, D., Palmer, D., Allen, C.D.C., Schmidt, T.H., Xu, Y., Proia, R., Coughlin, S.R. and Cyster, J.G. The sphingosine 1-phosphate receptor S1P2 maintains the homeostasis of germinal center B cells and promotes niche confinement. Nat. Immunol. 12: 672-680, 2011.
Suzuki, K., Grigorova, I., Phan, T.G., Kelly, L.M. and Cyster, J.G. Visualizing B cell capture of cognate antigen from follicular dendritic cells. J. Exp. Med. 206: 1485-1493, 2009
Suzuki, K., Kumanogoh, A. and Kikutani, H. Semaphorins and their receptors in immune cell interactions. Nat. Immunol. 9: 17-23, 2008.
Suzuki, K., Okuno, T., Yamamoto, M., Pasterkamp, R.J., Takegahara, N., Takamatsu, H., Kitao, T., Takagi, J., Rennert, P.D., Kolodkin, A.L., Kumanogoh, A. and Kikutani, H. Semaphorin 7A initiates T-cell-mediated inflammatory responses through α1β1 integrin. Nature 446: 680-684, 2007.


2016 Medical Research Encouragement Prize
(The Japan Medical Association)
2016 Astellas award for the best biomedical research
(The Astellas Foundation for Research on Metabolic Disorders)
2016 Astellas award for the outstanding presentation
(The Astellas Foundation for Research on Metabolic Disorders)
2012 Young Investigator Award
(The Japanese Society of Immunology)
2009 Inoue Research Award for Young Scientists
(The Inoue Foundation for Science)
2008 Long-term Fellowship
(Human Frontier Science Program)
2008 The Yamamura Prize
(Graduate School of Medicine, Osaka University)
2003 The Yamamura Prize
(Medical School of Osaka University)