The emerging role of neutrophils in autoimmune‐associated disorders: effector, predictor, and therapeutic targets

Abstract

Neutrophils are essential components of the immune system and have vital roles in the pathogenesis of autoimmune disorders. As effector cells, neutrophils promote autoimmune disease by releasing cytokines and chemokines cascades that accompany inflammation, neutrophil extracellular traps (NETs) regulating immune responses through cell–cell interactions. More recent evidence has extended functions of neutrophils. Accumulating evidence implicated neutrophils contribute to tissue damage during a broad range of disorders, involving rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary sjögren's syndrome (pSS), multiple sclerosis (MS), crohn's disease (CD), and gout. A variety of studies have reported on the functional role of neutrophils as therapeutic targets in autoimmune diseases. However, challenges and controversies in the field remain. Enhancing our understanding of neutrophils’ role in autoimmune disorders may further advance the development of new therapeutic approaches.

Tyrosine phosphatase SHP2 exacerbates psoriasis‐like skin inflammation in mice via ERK5‐dependent NETosis

“… 6 , 7 , 8 As the most abundant cells in innate immune cells, neutrophils also play an essential role in the occurrence and development of psoriasis. 9 , 10 …”

“…[6][7][8] As the most abundant cells in innate immune cells, neutrophils also play an essential role in the occurrence and development of psoriasis. 9,10 The traditional defense mechanisms of neutrophils include pathogen phagocytosis, degranulation, and cytokine production. Studies have recently found that neutrophils can undergo a unique cell death process called "NETosis" when stimulated by inflammatory factors, chemicals, or metabolites.…”

“…The dysfunctional immune system has been demonstrated to be a feature of psoriasis skin lesions and serves as the primary entrance point for study into the pathogenesis of psoriasis 6–8 . As the most abundant cells in innate immune cells, neutrophils also play an essential role in the occurrence and development of psoriasis 9,10 …”

Blockade of mIL‐6R alleviated lipopolysaccharide‐induced systemic inflammatory response syndrome by suppressing NF‐κB‐mediated Ccl2 expression and inflammasome activation

“…The results showed that the IL‐6R mAbs remarkably decreased ALT and AST levels in the serum (Figure 3C). Furthermore, to determine the inflammation of the lung tissue, we detected levels of myeloperoxidase (MPO), the sensitive biomarker associated with neutrophil accumulation‐mediated tissue injury in lung tissues 28,29 . The results suggested that MPO levels were significantly lowered in the h‐mIL‐6R mAb‐ and Tocilizumab‐treated SIRS mice (Figure 3D), suggesting that inflammation in lung tissue was lessened by the IL‐6R mAbs.…”

“…Furthermore, to determine the inflammation of the lung tissue, we detected levels of myeloperoxidase (MPO), the sensitive biomarker associated with neutrophil accumulation-mediated tissue injury in lung tissues. 28,29 The results suggested that MPO levels were significantly lowered in the h-mIL-6R mAb-and Tocilizumab-treated SIRS mice (Figure 3D), suggesting that inflammation in lung tissue was lessened by the IL-6R mAbs. Given that kidney injury is frequently complicated with SIRS, we detected blood urea nitrogen (BUN) and creatinine levels to evaluate the alterations of the renal function in the murine SIRS model.…”