Immune Regulation
Members
- Professor
- Katsuyuki Yui
- Associate Professor
- Shusaku Mizukami
- Assistant Professor
- Jiun Yu Jian
- Research Fellow
- Sukhbaatar Odsuren
- Assistant
- Mayumi Taniguchi
- Assistant
- Akiko Noguchi
･Mizukami Group
Activities
Our scope is the human immune response against malaria, and malaria vaccine development.
The life cycle of Plasmodium parasites which causes malaria can be divided into liver-（pre-erythrocytic）stage and erythrocytic-stage in human body. And, parasites show significant morphological change at each stage.
Although many vaccine development studies for malaria have been conducted, and there are already WHO-prequalified vaccines, RTS,S/AS-01 and R21/Matrix-M, it is considered that neither their effectiveness nor their supply capacity is sufficient. So, further development of malaria vaccine is required.
Cellular immunity, mediated by T lymphocytes, is considered having crucial roles on the defense against liver-stage malaria. However, most of the previous vaccine development studies have aimed to induce humoral immunity, mediated by antibodies, and there have not been many studies focusing on cellular immunity.
Our vaccine development has focused on tissue-resident memory T cells (TRM) in liver. Unlike circulating memory T cells, TRM reside in specific tissues or organs. We have confirmed the importance of TRM in the protective immunity against liver-stage malaria. Additionally, we have successfully induced sufficient numbers of TRM and observed protection in our mouse malaria model using mRNA-containing lipid nanoparticles (mRNA-LNP). Based on these findings, our malaria vaccine development is on-going.
Recent main research achievement
- Nakamae et al. Front Immunol 2023; 14: 1116299.
- Tayama et al. Trop Med Health 2023; 51(1): 12.
- Mizuta et al. Chem Med Chem 2023; 18(7): e202200586.
- Kawaguchi et al. J Phram Sci 2023; 112(5): 1401-1410.
- Kamiya et al. Pharamaceutics 2022; 14(11): 2357.
Achievement list
･Yui Group
Activities
Individuals living in the malaria endemic regions acquire resistance to infection and disease after repeated infection over time through the development of host immune responses. Persistent infection contributes for the maintenance of immunological memory, which effectively controls re-infection. However, it remains unclear how the maintenance of immunological memory to malaria is regulated during chronic infection. We perform the following research projects aiming for the development of next generation malaria vaccine and for the control of malaria re-infection in the areas of declining transmission
(1) Regulation of Immunological memory to malariaby IL-27
We investigate the mechanisms underlying the regulation of immunological memory to malaria using mouse models. We found that regulatory cytokine, IL-27, plays pivotal role in the regulation of immunological memory and investigate its underlying mechanisms.
(2) The field study on the maintenance of immunological memory to malaria in areas of declining transmission
Malaria cases are declining due to the effective measures in Asian countries. However, since the risk of re-infection is maintained, it is important to evaluate the maintenance of immunological memory to malaria in these regions. In collaboration with RITM in the Philippines and LSHTM in UK, we investigate the maintenance of memory lymphocytes specific for malaria antigens in individuals living in the different levels of malaria transmission in the Philippines.
Recent main research achievement
- Macalinao et al. EMBO Mol Med 2023; 15 (12): 10.15252/emmm.202317713.
- Ganley et al. Nature Immunol 2023; 24 (9): 1487‒1498.
- Macalinao et al. Lancet Reg Health West Pac 2023; 10.1016/j.lanwpc.2023.100792.
- Ntita et al. Int Immunol 2022; 34: 21-33.
- Enders et al. Curr Res Immnol 2021; 2: 79-92.