Neutrophil extracellular traps activate lung fibroblast to induce polymyositis‐related interstitial lung diseases via TLR9‐miR‐7‐Smad2 pathway

Zhang, Sigong; Jia, Xue-Qin; Zhang, Qiuyue; Zhang, Li; Yang, Jing; Hu, Caihong; Shi, Junnian; Xiao, Jianru; Lu, Jinyue; Shen, Hongfang

doi:10.1111/jcmm.14858

Cited by 55 publications

(40 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies show a closely relationship between NET and CTGF. Myofibroblast CTGF expression is enhanced by NETs inducer ( 45 ), which also promote lung fibroblasts activation and myofibroblast differentiation ( 45 , 46 ). Fibrotic interstitial lung biopsies demonstrate a close proximity between NETs and alpha-smooth muscle actin (α-SMA)-expressing fibroblasts ( 45 ).…”

Section: Neutrophils As Defenders and As Inducers Of Chronic Inflammation And Fibrosis Of The Lungmentioning

confidence: 99%

Neutrophils Modulate Fibrogenesis in Chronic Pulmonary Diseases

et al. 2021

View full text Add to dashboard Cite

Chronic inflammatory pulmonary diseases are characterized by recurrent and persistent inflammation of the airways, commonly associated with poor clinical outcomes. Although their etiologies vary tremendously, airway neutrophilia is a common feature of these diseases. Neutrophils, as vital regulators linking innate and adaptive immune systems, are a double-edged sword in the immune response of the lung involving mechanisms such as phagocytosis, degranulation, neutrophil extracellular trap formation, exosome secretion, release of cytokines and chemokines, and autophagy. Although neutrophils serve as strong defenders against extracellular pathogens, neutrophils and their components can trigger various cascades leading to inflammation and fibrogenesis. Here, we review current studies to elucidate the versatile roles of neutrophils in chronic pulmonary inflammatory diseases and describe the common pathogenesis of these diseases. This may provide new insights into therapeutic strategies for chronic lung diseases.

show abstract

Section: Neutrophils As Defenders and As Inducers Of Chronic Inflammation And Fibrosis Of The Lungmentioning

confidence: 99%

Neutrophils Modulate Fibrogenesis in Chronic Pulmonary Diseases

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Analogously, MCs have been shown to infiltrate lung and vascular tissue in pulmonary hypertension and lung fibrosis [ 88 ]. Notably, pathological remodeling in these diseases could be attenuated or prevented not only by mast cell stabilizers or in mast cell deficient animals [ 89 , 90 ], but also—at least in vitro—by DNase treatment [ 91 , 92 ], suggesting a potential pathogenic contribution of MCETs. Interrupting the formation of MCETs may also act as a successful strategy of pathogens to evade the MC-mediated immune response.…”

Section: Discussionmentioning

confidence: 99%

Significance of Mast Cell Formed Extracellular Traps in Microbial Defense

Komi

Kuebler

2021

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

Mast cells (MCs) are critically involved in microbial defense by releasing antimicrobial peptides (such as cathelicidin LL-37 and defensins) and phagocytosis of microbes. In past years, it has become evident that in addition MCs may eliminate invading pathogens by ejection of web-like structures of DNA strands embedded with proteins known together as extracellular traps (ETs). Upon stimulation of resting MCs with various microorganisms, their products (including superantigens and toxins), or synthetic chemicals, MCs become activated and enter into a multistage process that includes disintegration of the nuclear membrane, release of chromatin into the cytoplasm, adhesion of cytoplasmic granules on the emerging DNA web, and ejection of the complex into the extracellular space. This so-called ETosis is often associated with cell death of the producing MC, and the type of stimulus potentially determines the ratio of surviving vs. killed MCs. Comparison of different microorganisms with specific elimination characteristics such as S pyogenes (eliminated by MCs only through extracellular mechanisms), S aureus (removed by phagocytosis), fungi, and parasites has revealed important aspects of MC extracellular trap (MCET) biology. Molecular studies identified that the formation of MCET depends on NADPH oxidase-generated reactive oxygen species (ROS). In this review, we summarize the present state-of-the-art on the biological relevance of MCETosis, and its underlying molecular and cellular mechanisms. We also provide an overview over the techniques used to study the structure and function of MCETs, including electron microscopy and fluorescence microscopy using specific monoclonal antibodies (mAbs) to detect MCET-associated proteins such as tryptase and histones, and cell-impermeant DNA dyes for labeling of extracellular DNA. Comparing the type and biofunction of further MCET decorating proteins with ETs produced by other immune cells may help provide a better insight into MCET biology in the pathogenesis of autoimmune and inflammatory disorders as well as microbial defense.

show abstract

“…Recently neutrophils and NETosis have been shown to play important roles in lung inflammation. In autoimmune lung inflammation for example, NETs have been shown to activate lung fibroblasts and promote their proliferation and differentiation into myofibroblasts and thus contribute to interstitial lung disease in patients with poly-and dermato-myositis (28,29). In the pristaneinduced DAH model, treatment of mice with recombinant DNase I reduced NET formation and reduced lung pathology (17).…”

Section: Discussionmentioning

confidence: 99%

Neutrophils contribute to ER stress in lung epithelial cells in the pristane-induced diffuse alveolar hemorrhage mouse model

Tumurkhuu

et al. 2021

Preprint

View full text Add to dashboard Cite

Diffuse alveolar hemorrhage (DAH), although rare, is a life-threatening complication of systemic lupus erythematosus (SLE). Little is known about the pathophysiology of DAH in humans, although increasingly neutrophils, NETosis and inflammatory monocytes have been shown to play an important role in the pristane-induced model of SLE which develops lung hemorrhage and recapitulates many of the pathologic features of human DAH. Using this experimental model, we asked whether endoplasmic reticulum (ER) stress played a role in driving the pathology of pulmonary hemorrhage and what role infiltrating neutrophils had in this process. Analysis of lung tissue from pristane-treated mice showed genes associated with ER stress and NETosis were increased in a time-dependent manner and reflected the timing of CD11b+Ly6G+ neutrophil accumulation in the lung. Using precision cut lung slices from untreated mice we observed that neutrophils isolated from the peritoneal cavity of pristane-treated mice could directly induce the expression of genes associated with ER stress, namely Chop and Bip. Mice which had myeloid-specific deletion of PAD4 were generated and treated with pristane to assess the involvement of PAD4 and PAD4-dependent NET formation in pristane-induced lung inflammation. Specific deletion of PAD4 in myeloid cells resulted in decreased expression of ER stress genes in the pristane model, with accompanying reduction in IFN-driven genes and pathology. Lastly, coculture experiments of human neutrophils and human lung epithelial cell line (BEAS-2b) showed neutrophils from SLE patients induced significantly more ER stress and interferon-stimulated genes in epithelial cells compared to healthy control neutrophils. These results support a pathogenic role of neutrophils and NETs in lung injury during pristane-induced DAH through the induction of ER stress response and suggest that overactivation of neutrophils in SLE and NETosis may underlie development of DAH.

show abstract

Neutrophil extracellular traps activate lung fibroblast to induce polymyositis‐related interstitial lung diseases via TLR9‐miR‐7‐Smad2 pathway

Cited by 55 publications

References 44 publications

Neutrophils Modulate Fibrogenesis in Chronic Pulmonary Diseases

Neutrophils Modulate Fibrogenesis in Chronic Pulmonary Diseases

Significance of Mast Cell Formed Extracellular Traps in Microbial Defense

Neutrophils contribute to ER stress in lung epithelial cells in the pristane-induced diffuse alveolar hemorrhage mouse model

Contact Info

Product

Resources

About