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In a collaboration with scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), Kennedy researchers have contributed to the discovery that neutrophils have many more functions in the body than previously thought. This finding suggests that neutrophil tissue-specific plasticity could be exploited in designing new treatments for neutrophil driven diseases, including cancer.

Artistic representation of a neutrophil, the most abundant cell type in the innate immune system
Artistic representation of a neutrophil, the most abundant cell type in the innate immune system

In a study published in the journal Cell, the research team demonstrate that neutrophils, the most abundant cell type of the innate immune system, acquire new characteristics depending on the tissue they inhabit and that these specialised functions help to maintain organ health.

Professor Irina Udalova and her team at the Kennedy Institute contributed to this project by identifying stable modifications in the neutrophil chromatin landscape as cells transition from bone marrow or spleen into the blood, and between blood and the lung. Chromatin is a complex of DNA and proteins found within chromosomes that is modified by enzymes to help define and maintain the identity of a cell. Using a method called ATAC-seq, Irina and her team examined neutrophil chromatin accessibility, which revealed that neutrophils take on distinct states in different types of tissue.

Neutrophils are well known to provide non-specific defence against microbes and tissue damage.  However, due to their typically short lifespan of less than 24 hours, scientists have believed that these cells have limited capacity to adapt to their environment and adopt new functions.

But the new study shows that when neutrophils leave the blood and migrate into tissues they acquire new, previously unknown properties.

Dr Andrés Hidalgo at CNIC who is lead investigator on the study said, “What is fascinating is that neutrophils appear to acquire functions useful to the specific tissues in each organ. For example, we found that neutrophils in the lung acquire the ability to contribute to the formation of blood vessels, whereas neutrophils in the skin help to maintain the integrity of the cutaneous epithelium. This ability to change cell properties was identified in healthy individuals, which suggests that neutrophils participate in a great variety of normal functions in the body and are not limited to combating infection”.

Previous studies had already identified neutrophil heterogeneity in several diseases. Indeed, these neutrophil changes are prognostic markers in cancer and help to regenerate blood cells after bone marrow transplantation.

However Irina says the ability of neutrophils to transcriptionally reprogram has been overlooked. “This collaborative study makes the first step into understanding neutrophil adaptation to tissue environment at homeostasis. Further investigation into neutrophil transcriptional reprogramming in tissues under inflammatory duress, and decoding the molecular mechanisms and transcription factors that may orchestrate these responses, should be the next critical step.” she explains.

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