Unlike most cells with round nuclei, neutrophils (immune system cells floating in our blood) have nuclei with a complex lobular shape. Thanks to them, neutrophils can penetrate places that cells with normal nuclei cannot penetrate. The authors of a new article in the journal Nature have learned how such strange nuclei form and propose using this mechanism as a new form of therapy.

Among the blood cells that protect a person from infections, leukocytes are the most numerous neutrophils. They belong to the so-called innate immunity and are directly involved in the destruction (phagocytosis) of intruders – various pathogens, such as bacteria or viruses.

Unlike some other formed elements of the blood (mature erythrocytes and platelets), neutrophils do not have a nucleus, but their shape is quite unusual. If in most cells the nucleus is round or oval, in neutrophils it is lobed, that is, it consists of several sections connected by ligaments.

The structure of the nucleus is markedly different in maturing (rod nuclear) and mature (segment nuclear) neutrophils. This unusual modification of immune cells makes them highly mobile. Neutrophils, thanks to their flexible nuclei, can “climb” into any tissue into which any cell with a rounded nucleus can squeeze. It is not difficult to guess that pathogens and places of inflammation serve the target.

Authors of the article in a leading scientific journal Nature discovered the mechanisms by which neutrophils change the shape of their nuclei. Scientists used selective staining of cells and identified changes in the conformation (i.e. three-dimensional shape) of chromosomes in neutrophil precursor cells.

It turns out that the basis for the unique shape of the nuclei is the inhibition of the DNA packaging mechanism called “loop extrusion (or push through) loops.” It contains special “molecular engines”, in particular the cohesin protein complex.

By eliminating the NIPBL (folded B-like protein) factor required for loop extrusion, the scientists caused unusual changes in the shape of the nucleus in neutrophil precursor cells: horseshoe, ribbon, ring, etc. They took shape. The authors believe this corresponds to what happens to cells during normal differentiation of neutrophils; neutrophils thus acquire a unique chromatin architecture and package their chromosomes into structures resembling lobules or petals. NIPBL deficiency also stopped cell division and activated specific genes active in neutrophils.

The authors hope that their results have more than theoretical significance and may become the basis for new treatment methods. By artificially giving cell nuclei an unusual shape, we will be able to improve their ability to penetrate the thickness of tissues and, as a result, kill infectious agents more effectively.