Emerging roles of neutrophils in immune homeostasis

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. [BMB Reports 2022; 55(10): 473-480]

Biomaterials for immunomodulation in wound healing

“…However, this robust response aimed at combating microbial invaders can potentially result in excessive inflammation and impaired wound healing. Apoptotic neutrophils release signaling molecules such as phosphatidylserine that promote phagocytosis and subsequent interactions with macrophages, leading to the development of a repair macrophage phenotype characterized by the production of transforming growth factor-beta (TGF-β) and IL-10 [ 36 ]. For example, Jin’s group developed engineered neutrophil apoptotic bodies to mimic the role of apoptotic neutrophils in reprogramming macrophages and resolving inflammation [ 37 ].…”

Immunology of chronic low-grade inflammation: relationship with metabolic function

“…During this process, lysosomal degradation of apoptotic bodies through catabolism of cell corpses furthermore provides substrates for the metabolic switch to favour oxidative phosphorylation and triggers various nuclear transcription factors to induce the transcription of immunosuppressive cytokines such as IL10 and transforming growth factor-β (Zhang et al 2019b). Disruption of efferocytosis as seen in metabolic disorders, such as diabetes, results in the accumulation of necrotic/pyroptotic neutrophil bodies which aggravate inflammation through increased activation of M1 macrophages, dendritic cells, and Th1/Th17 lymphocyte responses (Lee et al 2022, Mahmoudi et al 2022. In addition to continuous activation signals observed in obesity and diabetes, given the importance of intracellular metabolism in determining macrophage function, aberrant activation and reprogramming of macrophages also occur due to metabolic disturbances (An et al 2019, Mahmoudi et al 2022.…”

Transfusion support in hematopoietic stem cell transplantation

“…Granulocytes are white blood cells involved in the innate immune system. They perform phagocytosis, produce reactive oxygen species, release cytokines and chemokines, and are related to neutrophil extracellular traps [ 52 - 54 ]. Granulocyte transfusion (GT) can be administered to patients undergoing chemotherapy or HSCT for infection control.…”