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, hoping to provide a precise overview of neutrophil functions in the pathogenesis of IBD.

Keywords: immune response; inflammatory bowel disease; innate immune cell; intestinal inflammation; microbial dysbiosis; mucosal homeostasis; neutrophil.

Figure 1.

The ‘yin’ and ‘yang’ of neutrophil functions in the pathogenesis of IBD. Neutrophils not only participate in the mucosal injury, aberrant responses to icrobiota, extensive intestinal inflammation, and therapeutic failure in IBD, but also play an important role in the elimination of pathogens, angiogenesis and wound healing, which is a prerequisite for the restoration of intestinal inflammation. All this knowledge elucidates the beneficial and deleterious roles of neutrophils in the pathogenesis of IBD.