Discovery of a molecule regulating immune memory of natural killer cells to viral infection

Tsukuba, Japan—Viral infections pose a severe threat to human health, with natural killer (NK) cells acting as the primary defense against virus-infected cells. Following a viral invasion, the immune system retains a memory of the virus, thereby persisting in the body for a long time. However, it was believed that NK cells could not differentiate into immune memory NK cells capable of robustly combating subsequent viral invasions. Recent research challenges this established theory, revealing that NK cells can indeed memorize viral antigens and differentiate into immune memory NK cells with considerable killing ability. However, the mechanism of this process still needs to be fully clarified.

The research team uncovered that Themis2, located in the cytoplasm of NK cells, plays a crucial role in regulating the differentiation and function of immune memory NK cells. Specifically, NK cells deficient in Themis2 exhibit a more efficient differentiation into immune memory NK cells following cytomegalovirus infection compared to wild-type NK cells. Furthermore, Themis2-deficient immune memory NK cells can efficiently eliminate cytomegalovirus-infected cells. These findings suggest the possible development of a novel therapeutic approach to viral infections by targeting Themis2 to enhance the differentiation and function of immune memory NK cells.

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This work was supported by JSPS KAKENHI 16H06387, 18H05022, and 21H04836 (A.S.), 17H05071, JST FOREST JPMJFR2166, the Japanese Society for Immunology Outstanding Young Immunology Researcher Award, University of Tsukuba Seeding Program for Research, and Tsukuba Basic Research Support Program (T.N.)

_{Original Paper}

Title of original paper:
Themis2 regulates natural killer cell memory function and formation

Journal:
Nature Communications

DOI:
10.1038/s41467-023-42578-8

_{Correspondence}

Professor SHIBUYA, Akira
Institute of Medicine, University of Tsukuba

Assistant Professor NABEKURA, Tsukasa
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba

_{Related Link}

Institute of Medicine