BMB Reports 2022; 55(10): 473-480  https://doi.org/10.5483/BMBRep.2022.55.10.115
Emerging roles of neutrophils in immune homeostasis
Mingyu Lee1, Suh Yeon Lee2 & Yoe-Sik Bae1,2,*
1Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06355, 2Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Korea
Correspondence to: Tel: +82-31-290-5914; Fax: +82-31-290-7015; E-mail: yoesik@skku.edu
Received: July 25, 2022; Revised: August 12, 2022; Accepted: August 23, 2022; Published online: October 31, 2022.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Neutrophils, the most abundant innate immune cells, play essential roles in the innate immune system. As key innate immune cells, neutrophils detect intrusion of pathogens and initiate immune cascades with their functions; swarming (arresting), cytokine production, degranulation, phagocytosis, and projection of neutrophil extracellular trap. Because of their short lifespan and consumption during immune response, neutrophils need to be generated consistently, and generation of newborn neutrophils (granulopoiesis) should fulfill the environmental/systemic demands for training in cases of infection. Accumulating evidence suggests that neutrophils also play important roles in the regulation of adaptive immunity. Neutrophil-mediated immune responses end with apoptosis of the cells, and proper phagocytosis of the apoptotic body (efferocytosis) is crucial for initial and post resolution by producing tolerogenic innate/adaptive immune cells. However, inflammatory cues can impair these cascades, resulting in systemic immune activation; necrotic/pyroptotic neutrophil bodies can aggravate the excessive inflammation, increasing inflammatory macrophage and dendritic cell activation and subsequent TH1/TH17 responses contributing to the regulation of the pathogenesis of autoimmune disease. In this review, we briefly introduce recent studies of neutrophil function as players of immune response.
Keywords: Efferocytosis, Granulopoiesis, Immune homeostasis, Neutrophil, Resolution
FIGURE
Fig. 1. Function of neutrophils and their generation (granulopoiesis). Neutrophils circulate and detect inflammatory cues. (A) Because of their short lifespan, neutrophils are continuously generated in the bone marrow of the hematopoietic system by granulopoiesis. (B) When they detect alert signals from inflamed tissue, neutrophils transmigrate into inflamed sites and initiate immune activation. (C) Sensing the size of pathogens by means of dectin-1, non-TLR pattern recognition receptor, and distinct generation of reactive oxygen species (ROS), neutrophils may surround pathogens (swarming), prey on them (phagocytosis), or project a sticky neutrophil extracellular trap (NET), while secreting context-dependent cytokines and granules (degranulation). (D, E) Self-immolation of neutrophils (D) and immune activation of other monocytes and macrophages (Mϕ) increases production of IL-6, G-CSF, and GM-CSF, which in turn stimulate emergency neutrophil generation in the bone marrow (granulopoiesis) (E) and spleen (not shown). The context and signaling cues given for granulopoiesis affect the heterogeneity of newly generated neutrophils (trained granulopoiesis).

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