Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases

Abstract

Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis. They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation, but paradoxically, they also limit exogenous microbial invasion and facilitate mucosal restoration. Hyperactivation or dysfunction of neutrophils results in abnormal immune responses, leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases (IBD). As a refractory intestinal inflammatory disease, the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved. However, the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood. Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis, aggravated intestinal architectural damage, compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD. Paradoxically, activated neutrophils are also associated with effective elimination of invaded microbiota, promoted angiogenesis and tissue restoration of gut mucosa in IBD. Here, we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinal mucosal inflammation and provide a precise overview of neutrophil functions in the pathogenesis of IBD.

Isobaric labeling‐based quantitative proteomics of FACS‐purified immune cells and epithelial cells from the intestine of Crohn's disease patients reveals proteome changes of potential importance in disease pathogenesis

“…The other is proteins associated with neutrophil degranulation. This is also consistent with CD pathophysiology, as influx of neutrophils contributes to perpetuating inflammation and mucosal damage, although they also may have beneficial effects [19].…”

Single cell analysis via mass cytometry of spontaneous intestinal perforation reveals alterations in small intestinal innate and adaptive mucosal immunity

“…Neutrophils play an important role in maintaining intestinal homeostasis and are recruited to sites of active inflammation ( 31 ). They have both pro- and anti-inflammatory effects in the intestinal mucosa and are essential in the early phase of pathogen encounter and recruit other immune cells to the site of inflammation ( 32 ). Neutrophil migration to colon has been described in inflammatory bowel diseases and correlates to disease severity ( 33 ).…”

Role of CD34 in inflammatory bowel disease

“…Neutrophils and eosinophils are most closely related to the development of IBD ( Siel et al, 2022 ). Neutrophils are components of the innate immune system and their recruitment and aggregation during IBD occur in the intestinal mucosa ( Sadik et al, 2011 ; Chen et al, 2021 ). They have both positive and negative effects on IBD; on the one hand, they promote the repair of mucosal inflammatory injury by removing harmful pathogens ( Sumagin et al, 2016 ).…”

“…On the other hand, they are involved in the occurrence and aggravation of inflammation in the intestinal mucosal by participating in the excessive immune response ( Wandall, 1985 ; de Bont et al, 2020 ). Neutrophil recruitment and infiltration in the intestinal mucosa of patients with IBD is the result of the combination of cytokines and chemokines presence ( Chen et al, 2021 ). Notably, the literature suggests that CD34 recruits neutrophils to the sites of inflammation ( Grassl et al, 2010 ; Lo et al, 2017 ).…”