Researchers from Universidad Carlos III de Madrid (UC3M), the National Center for Cardiovascular Research (CNIC), and Yale University (USA) have published a comprehensive review article in the journal Cell that proposes a new framework for understanding neutrophils, the most abundant cells of the immune system. Drawing on extensive evidence from recent research, the authors describe neutrophils as a dynamic and adaptable collective, capable of functional diversification and forms of immunological memory, far beyond their traditionally assigned roles.
By integrating findings from cancer, inflammation, and systems immunology, the Review reshapes how neutrophils are viewed in health and disease, and highlights new conceptual routes for the development of innovative therapeutic strategies targeting immune dysfunction.
“Neutrophils are the most abundant cells in the immune system and the first to respond in the body when an infection or injury occurs. But these cells not only help fight pathogens, they also repair tissues and aid in the formation of blood vessels”, explains Iván Ballesteros, professor in the Department of Neuroscience and Biomedical Sciences at UC3M and researcher at the CNIC, who has published this work together with Andrés Hidalgo, from the Department of Immunobiology at Yale University School of Medicine and also a researcher at the CNIC. “Therefore,” he continues, “if we want to understand how neutrophils work, we have to study them as a whole, as if they were an anthill: we cannot study what a worker ant or a soldier ant does separately; we have to understand how the cells coordinate and what role each one plays”.
Traditionally, neutrophils have been described as cells specialized in the rapid elimination of pathogens and with a very limited lifespan. However, the authors propose that these cells have a remarkable ability to adapt to different tissues and contexts, participate in processes such as sterile inflammation, tissue repair, or cancer, and exhibit coordinated collective behaviors similar to those observed in other biological systems.
The researchers emphasize that this new conceptual framework may help reinterpret the role of neutrophils in numerous diseases, from cancer to inflammatory or autoimmune pathologies. In this sense, it could open up new therapeutic avenues aimed at modulating their production and functional programming. “The study highlights that neutrophils are not mere executors of immediate immune responses, but a highly organized, plastic system with memory, whose therapeutic potential is still far from being exploited”, adds Andrés Hidalgo.
This study proposes that the neutrophil population is organized into two interconnected functional compartments: one “granulopoietic”, located mainly in the bone marrow and responsible for neutrophil production; and another “mature”, consisting of already differentiated cells circulating in the blood and tissues. This organization would allow the system to respond quickly to local aggressions, while maintaining a memory of previous exposures.
According to the model proposed by the researchers, this structure explains how neutrophils can exhibit great functional diversity, adapt to local signals from different organs, and participate in processes as varied as angiogenesis, immune response regulation, and tissue homeostasis maintenance. In addition, the authors emphasize that many of these properties emerge only when the neutrophil collective is considered as a biological unit, rather than as individual cells.
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