University of Dundee

Protein family found to affect neutrophil development

27 May 2020

New research uncovers part of the intricate control that takes place during the development of important members of our immune system, neutrophils. This work was published this week in eLife.

Neutrophils are the most abundant immune cells in humans and are essential to defend our body against infections. They develop in the bone marrow in a process called granulopoiesis which occurs at a high turnover during steady state and at even higher rates during infection or inflammation. This new work has found that a protein family called linker histones affects granulopoiesis.

The publication first author, new group leader Gabriel Sollberger based in Cell Signalling and Immunology, completed this work during his previous position as a postdoctoral researcher in the lab of Arturo Zychlinsky at the Max Planck Institute for Infection Biology in Berlin, Germany.

Gabriel explains, “Our aim was to identify novel regulators of neutrophil maturation and function. This is important, since inappropriate neutrophil activation can cause tissue damage whereas a failure to activate neutrophils leads to high susceptibility to infections. We found by using a genetic screen that specific subtypes of linker histones affect the differentiation of neutrophils. This is an exciting and novel addition to the field of granulopoiesis.”

The study was the first to use a genetic screen to investigate human neutrophil maturation and function. The researchers used the human myeloid cell line PLB-985 and a genome-wide CRISPR/Cas9 loss of function screen, thereby demonstrating that neutrophil-like cells are a suitable tool to study neutrophil mechanisms by such approaches.

“We found that specific linker histone subtypes affect the lineage choice and subsequent differentiation of hematopoietic precursor cells into neutrophils. Our work, which has mainly been done in a human cell line, might lead to new research investigating the role of other linker histone subtypes in the differentiation of immune cells in vivo, which would help our understanding of hematopoiesis and, possibly, could also lead to research investigating the role of linker histones in infections and disease” concluded Gabriel.

Read the study in eLife: https://elifesciences.org/articles/52563

Image: Transmission electron microscopy image showing the myeloid cell line PLB-985 after differentiation, when cells acquire a neutrophil-like nucleus, granules and become able to perform neutrophil functions. Figure 1a, panel d7.

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