Human Immunology （Single Cell Genomics)
TEL +81-6-6879-4935(IFReC lab) +81-6-6879-8323 (Biken lab)
Overview
Analysis of NK Cell Diversification and Adaptive Differentiation Mechanisms During the Recovery Phase of Severe COVID-19
Natural killer (NK) cells are innate lymphocytes responsible for the early defense against viral infections and cancer. In recent years, it has been reported that, following infections such as cytomegalovirus infection, NK cells can differentiate into so-called “adaptive NK cells” that acquire memory-like immune properties. Using single-cell RNA sequencing, our research group conducted a comprehensive comparative analysis of NK cell responses in mRNA vaccine recipients and in patients with severe COVID-19. We found that while vaccination led to an increase in immature NK cells, the recovery phase from severe COVID-19 selectively induces adaptive NK cells with potent cytotoxic activity (Fig. 1). Furthermore, through trajectory analysis we identified a branch point during NK cell maturation at which cell fate is determined toward either a “canonical” or an “adaptive” lineage. We revealed that differentiation toward the adaptive lineage involves the expression of genes related to T-cell receptor signaling and metabolic reprogramming. This study aims to elucidate the mechanisms of NK cell diversification in response to the environment for the development of novel immunomodulatory strategies against infectious diseases and cancer.
Fig. 1
Principal Investigator
Daisuke Okuzaki Associate Professor
Research field
Bioinformatics, immunology, genome informatics
Education history
| 1995.3 | BSc, Faculty of Engineering, Okayama University, Japan |
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| 1997.3 | MEng, Graduate School of Engineering, Okayama University, Japan |
| 2001.3 | PhD, Osaka University, Japan |
Research and career history
| 2002.1 | Assistant, Research Institute for Microbial Diseases, Osaka University |
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| 2004.4 | DNA Chip Development Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University |
| 2004.4 | Assistant, Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University (until 2007.3) |
| 2007.4 | Assistant Professor, DNA Chip Development Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University |
| 2017.4 | Assistant Professor, NGS Core, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University |
| 2019.4 | Integrated Frontier Research for Medical Science Division (concurrent), Institute for Open and Transdisciplinary Research Initiatives, Osaka University |
| 2019.11 | Specially Appointed Associate Professor, Immunology Frontier Research Center (IFReC), Osaka University |
| 2019.11 | Specially Appointed Associate Professor (concurrent), Next-Generation (NGS) Core Facility, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University |
| 2021.4 | Concurrent center and academic staff, Graduate School of Medicine, Center for Infectious Disease Education and Research, Osaka University |
| 2023.7 | Team of Clinical and Translational Research (concurrent), Center for Advanced Modalities and DDS, Osaka University |
| 2024.10 | Bioinformatics Center (concurrent), Research Institute for Microbial Diseases, Osaka University |
| 2024.11 | Advanced Data Science Center for Protein Research (concurrent), Osaka University |
Members
- Daisuke Okuzaki Associate Professor
dokuzakiifrec.osaka-u.ac.jp - Mohamad Al kadi Specially Appointed Researcher
malkadiifrec.osaka-u.ac.jp
Achievements
Publications
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Ito, H., Ishikawa, M., Yoshimura, J., Liu, Y., Sakakibara, S., Sugihara, F., Matsumoto, H., Hirata, H., Ogura, H., Oda, J. & Okuzaki, D. Neutrophil gene expression in COVID-19 patients with acute respiratory distress syndrome. Front. Immunol. 16, 1620745 (2025).
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Kishi, Y., Liu, Y. C., Ishikawa, M., Yamashita, M., Matsumoto, H., Ogura, H., Sakakibara, S. & Okuzaki, D. Mapping NK cell diversity in response to COVID-19 and mRNA vaccination. Sci. Rep. 15, 37577 (2025).
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Al Kadi, M., Yamashita, M., Shimojima, M., Yoshikawa, T., Ebihara, H., Okuzaki, D. & Kurosu, T. Cytokine storm and vascular leakage in severe dengue: insights from single-cell RNA profiling. Life Sci. Alliance 8, e202403008 (2025).
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Liu, Y. C., Ishikawa, M., Sakakibara, S., Kadi, M. A., Motooka, D., Naito, Y., Ito, S., Imamura, Y., Matsumoto, H., Sugihara, F., Hirata, H., Ogura, H. & Okuzaki, D. Full-length nanopore sequencing of circular RNA landscape in peripheral blood cells following sequential BNT162b2 mRNA vaccination. Gene 933, 148971 (2025).
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Sakakibara, S., Liu, Y. C., Ishikawa, M., Edahiro, R., Shirai, Y., Haruna, S., El Hussien, M. A., Xu, Z., Li, S., Yamaguchi, Y., Murakami, T., Morita, T., Kato, Y., Hirata, H., Takeda, Y., Sugihara, F., Naito, Y., Motooka, D., Tsai, C. Y., Ono, C., Matsuura, Y., Wing, J. B., Matsumoto, H., Ogura, H., Okada, M., Kumanogoh, A., Okada, Y., Standley, D. M., Kikutani, H. & Okuzaki, D. Clonal landscape of autoantibody-secreting plasmablasts in COVID-19 patients. Life Sci. Alliance 7, e202402774 (2024).
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Kurosu, T., Okuzaki, D., Sakai, Y., Kadi, M. A., Phanthanawiboon, S., Ami, Y., Shimojima, M., Yoshikawa, T., Fukushi, S., Nagata, N., Suzuki, T., Kamimura, D., Murakami, M., Ebihara, H. & Saijo, M. Dengue virus infection induces selective expansion of Vγ4 and Vγ6TCR γδ T cells in the small intestine and a cytokine storm driving vascular leakage in mice. PLoS Negl. Trop. Dis. 17, e0011743 (2023).
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Ishikawa, M., Shimada, Y., Ozono, T., Matsumoto, H., Ogura, H., Kihara, K., Mochizuki, H., Okuno, T., Sakakibara, S., Kinoshita, M. & Okuzaki, D. Single-cell RNA-seq analysis identifies distinct myeloid cells in a case with encephalitis temporally associated with COVID-19 vaccination. Front. Immunol. 14, 998233 (2023).