Beyond the Human Body: Models for Studying Neutrophil Biology

Neutrophils are a key component of the immune system, integrating antimicrobial and immunomodulatory functions through various strategies, including phagocytosis, degranulation, generation of reactive oxygen species (ROS), and release of neutrophil extracellular traps (NETs). Owing to their complexity and involvement in a wide range of conditions, including autoimmune diseases, neutrophils have emerged as a major focus of biomedical research. However, it should be noted that neutrophil studies face significant challenges, including short lifespan, terminal differentiation, tendency to spontaneous activation, and donor variability. Moreover, resistance to genetic modifications limits the detailed investigation of gene function and signaling pathways in neutrophil biology. To overcome these constraints, a range of experimental models has been developed. In this review, we present a guide to the currently available neutrophil models (HSPC, iPSC, HL-60, PLB-985, NB4, Kasumi-1, ER-Hoxb8), highlighting their strengths and limitations, with particular emphasis on their value as genetically modifiable platforms. Additionally, we provide an insight into the mechanisms governing neutrophil effector functions.