Granulopoiesis and Neutrophil Homeostasis: A Metabolic, Daily Balancing Act. Issue 7 (July 2019)

• Record Type: Journal Article
• Authors: Yvan-Charvet, Laurent; Ng, Lai Guan
• Is Part Of: Trends in immunology. Volume 40:Issue 7(2019)
• Page Start: 598
• Page End: 612
• Publication Date: 2019-07
• Subjects: Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2019.05.004
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : Granulopoiesis is part of the hematopoietic hierarchic architecture, where hematopoietic stem cells give rise to highly proliferative multipotent and lineage-committed granulocytic progenitor cells that differentiate into unipotent neutrophil progenitors. Given their short lifespan, neutrophils are rapidly cleared from circulation through specialized efferocytic macrophages. Together with an intrinsic clock, these processes contribute to circadian fluctuations, preserving self-tolerance and protection against invading pathogens. However, metabolic perturbation of granulopoiesis and neutrophil homeostasis can result in low-grade chronic inflammation, as observed with aging. During acute pathogenic infections, hematopoiesis can also be switched into emergency mode, which has been recently associated with significant neutrophil functional heterogeneity. This review focuses on a new reassessment of regulatory mechanisms governing neutrophil production, life-cycle, and diversity in health and disease. Highlights: Granulopoiesis is a process by which neutrophils are generated. Emerging evidence suggests that this process is not a 'hard-wired' hierarchical program as previously thought, but rather, a continuum-based, step-wise process. Recent systematic phenotypic and molecular delineation of neutrophil subsets during their developmental trajectory has provided: (i) a fundamental framework to integrate and better understand granulopoiesis, and (ii) an improved characterization of neutrophil subsets at both steady and inflammatory states. Under resting conditions, granulopoiesis is regulated by a number of physiological processes, such as diurnal oscillation and metabolic and cell-intrinsic aging processes. In response to stress conditions, emergency granulopoiesis will be 'switched' on. Emerging evidence suggests that neutrophils generated from the bone marrow are functionally different from those derived from extramedullary sites such as the spleen, where splenic-derived neutrophils are more immunosuppressive.