Researchers at the Kennedy Institute have provided the most comprehensive overview to date of how the distinctive segmented nucleus of neutrophils influences their function in health and disease.
The review, published in Nature Reviews Immunology, connects decades of cellular and molecular studies to unravel the biological significance and underlying mechanisms of the neutrophil nucleus.
Neutrophils, the most abundant white blood cells in the human body, are essential components of the immune system, rapidly migrating to sites of infection and inflammation to destroy pathogens. A distinct feature of the mature neutrophil is its nucleus, divided into three or four lobes connected by thin filaments. The shape was first described as early as 1900, but its purpose has remained largely unknown.
Dr. Erinke van Grinsven, Dr. Ananda Mukherjee and Professor Irina Udalova from the Kennedy Institute systematically reviewed the latest evidence to explore why neutrophil nuclei are segmented and how this structure might contribute to their specialized roles.
Dr. van Grinsven said, “Scientists have pondered the segmented shape of the neutrophil for years but it’s only now that we begin to understand its purpose. We and others found that, along with changes in nuclear morphology as the neutrophil develops, there are coordinated changes in how the DNA is organized, which genes are active, and how the nuclear envelope is structured. It’s this process that prepares neutrophils for their key task of rapid migration through tight tissue spaces during the immune response to fight inflammation.”
The flexibility to squeeze through narrow gaps is governed by the distinct nuclear composition. Low levels of certain structural proteins, such as lamins, make the nuclear envelope more deformable, while dense chromatin (the mixture of DNA and proteins inside the nucleus) maintains DNA integrity.
Dr. Mukherjee said that he was particularly taken by the spatial organization of chromatin within the segmented nucleus that may also enable rapid switching between active and inactive genes during infection.
The researchers also highlight that abnormal nuclear shapes are seen in several diseases, from benign conditions like the Pelger-Huët anomaly to inflammatory and infectious diseases such as cancer and COVID-19 where neutrophil behavior is altered.
Professor Udalova added, “Understanding how nuclear structure governs neutrophil function may help explain why immature or abnormally shaped neutrophils contribute to tissue damage in inflammatory diseases. The interplay between nuclear architecture, gene regulation, and immune function opens new avenues for investigating neutrophil-related diseases.
“We hope that this systematic review of the state-of-the-art in the field will inspire new studies to connect this visual feature to modern molecular and functional understanding.”
More information:
Erinke van Grinsven et al, Shaping neutrophil morphology and function: the importance of a segmented nucleus, Nature Reviews Immunology (2025). DOI: 10.1038/s41577-025-01237-3
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