Unexpected behavior observed during interactions between immune cells and dying cells

Over the years, cell biology has built a detailed picture of how cells compartmentalize their internal functions. Central to this organization is the nucleus, which houses the genetic material and is separated from the cytoplasm by a robust nuclear envelope. Traditionally, the nuclear membrane has been considered a strict barrier, maintaining nuclear integrity except during carefully controlled processes such as mitosis. As a result, the release of nuclear material has largely been associated with cellular damage or death.

However, recent work by a research team in Japan suggests that this view may be incomplete. While investigating immune-related cellular responses, the researchers observed unexpected behavior during interactions between immune cells and dying cells. Using experimental approaches combined with advanced imaging techniques, they tracked the movement of nuclear components under specific stimuli. To their surprise, nuclear DNA was selectively extracted from the nuclei of dying cells in a controlled and repeatable manner, without classical nuclear envelope breakdown or whole-cell phagocytosis.

Recognizing that this process differed fundamentally from any known cellular mechanism, the team identified it as a new phenomenon and named it nucleocytosis. The research was led by Professor Ken J. Ishii from the Department of Microbiology and Immunology at the Institute of Medical Science, The University of Tokyo, Japan, along with Dr. Hideo Negishi, project lecturer, Mr. Yusuke Wada, researcher from the same institute, and Dr. Yoshitaka Shirasaki, associate professor at Research Center for Advanced Science and Technology, The University of Tokyo, Japan. Their findings were published in Nature Communications on February 18, 2026.

Further experiments showed that nucleocytosis is not a random event but a regulated cellular function. This suggests that immune cells may intentionally access nuclear DNA from dying cells as part of regulated immune signaling processes. Such extracted nuclear DNA could act as molecular messengers, alerting the immune system or shaping inflammatory responses in ways that were previously unrecognized.

"The most striking aspect of our findings was realizing that cells possess an entirely new way to handle nuclear contents," explains Dr. Negishi. "This discovery forces us to rethink how self-DNA activates immune response and how such activation can drive a variety of self-DNA-related diseases."

The implications of nucleocytosis extend well beyond basic cell biology. Because immune recognition of nuclear material plays a key role in autoimmune diseases, infections, and cancer, understanding this pathway may help clarify disease mechanisms that have long remained elusive. In addition, nucleocytosis could represent a new target for therapeutic intervention, offering opportunities to regulate immune responses more precisely.

The motivation behind the study was also shaped by recent global health challenges. "During the spread of the novel coronavirus, many antiviral drugs were reported, but their mechanisms were largely unknown," says Prof. Ishii. "I wanted to contribute to understanding how such drugs function at the cellular level and to support the development of new medications."

In the short term, the discovery of nucleocytosis is expected to influence how cell biology is taught, potentially appearing in future textbooks as a newly defined cellular function. Over the longer term, insights gained from this research may directly inform drug development strategies. Within the next five to ten years, a deeper understanding of nucleocytosis could support the design of therapies for immune-related diseases, infections, and cancer, ultimately translating fundamental science into tangible benefits for society.