About 150 years ago, scientists discovered that special blood cells play an important role in the immune system’s defense against infection and disease.

Certain groups of these white blood cells, now known as neutrophils, are characterized by a nucleus that differs markedly from most nuclei. The majority of cells have round or oval-shaped nuclei that are rigid, but neutrophils differ in that their nuclei adopt multiple lobular structures resembling the arrangement of flower petals.

These unique nuclear motifs allow neutrophils to travel throughout the body to identify and fight invading pathogens. Although much is now known about the role of neutrophils in fighting infection, how such strange nuclear structures are assembled has remained a mystery since the 1880s.

Reporting in The nature, University of California San Diego School of Biological Sciences Postdoctoral Scholar Indomathi Patta; Ming Ho at the Cleveland Clinic Foundation has deciphered the shape-shifting puzzle of the neutrophil nucleus.

“Now we know how these nuclear forms assemble and it’s a beautiful process,” said Morey, a distinguished professor in the Department of Molecular Biology.

Using a combination of an ancient staining method combined with modern techniques, called chromosome-conformation-capture studies, the researchers unveiled how flower-like nuclei assemble. While the chromosomes of round cells assemble into stacked bundles of DNA loops, the neutrophil genome lacks such loops. Remarkably, when the researchers removed the chromatin loops, the progenitor cells rapidly changed from round nuclear shapes to flower-petal arrangements similar to those found in neutrophils. This simple change is also sufficient to activate thousands of genes associated with the inflammatory gene program that allows neutrophils to fight invading bacteria.

Having unveiled the neutrophil loop assembly question, the researchers now believe they have instructions to guide the development of new nuclear forms.

“This potentially opens an exciting new chapter in immunotherapy because it should theoretically be possible to alter the nuclear structure of killer immune cells so that they can more easily attack complex, solid environments such as tumors,” Murray said. . “Fundamentally, this effect could lead to engineering novel nuclear forms in immune cells, a novel concept in therapeutic development.”

Authors of the study include: Indomathi Pata, Maryam Zand, Lindsay Lee, Shreya Mishra, Alexandra Bortnick, Hanbin Lu, Arpita Presti, Sarah McArdle, Zbigniew Mikulski, Huan Yu Wang, Christine Cheng, Kathleen Fish, Ming Hu and Cornelius Murray.