Spatiotemporal regulation of neutrophil heterogeneity in health and disease

Neutrophils are the most abundant leukocytes in humans and are indispensable for innate immunity. They are short-lived, terminally differentiated cells. However, mounting evidence indicates that neutrophils are heterogeneous in health and disease: they are young or aged in a steady state, while their heterogeneity becomes more diverse in disease conditions, such as cancer, sepsis, and thromboinflammation. Although the presence of distinct neutrophil subsets is well recognized, it is not fully understood how neutrophils have functional and phenotypic heterogeneity and what mechanisms control it. This review will focus on our current understanding of the molecular basis for neutrophil heterogeneity in pathophysiological conditions. In addition, we will discuss the possibility of targeting a specific subset of neutrophils to attenuate inflammation and tissue damage without compromising innate immune responses.