The Role of Tissue-Resident Macrophages in the Development and Treatment of Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, is a refractory disease with many immune abnormalities and pathologies in the gastrointestinal tract. Because macrophages can distinguish innocuous antigens from potential pathogens to maintain mucosa barrier functions, they are essential cells in the intestinal immune system. With numerous numbers in the intestinal tract, tissue-resident macrophages have a significant effect on the constant regeneration of intestinal epithelial cells and maintaining the immune homeostasis of the intestinal mucosa. They also have a significant influence on IBD through regulating pro-(M1) or anti-inflammatory (M2) phenotype polarization according to different environmental cues. The disequilibrium of the phenotypes and functions of macrophages, disturbed by intracellular or extracellular stimuli, influences the progression of disease. Further investigation of macrophages’ role in the progression of IBD will facilitate deciphering the pathogenesis of disease and exploring novel targets to develop novel medications. In this review, we shed light on the origin and maintenance of intestinal macrophages, as well as the role of macrophages in the occurrence and development of IBD. In addition, we summarize the interaction between gut microbiota and intestinal macrophages, and the role of the macrophage-derived exosome. Furthermore, we discuss the molecular and cellular mechanisms participating in the polarization and functions of gut macrophages, the potential targeted strategies, and current clinical trials for IBD.

Shared Genes of PPARG and NOS2 in Alzheimer’s Disease and Ulcerative Colitis Drive Macrophages and Microglia Polarization: Evidence from Bioinformatics Analysis and Following Validation

“…Macrophages are heterogeneous, plastic, and strongly influenced by the microenvironment [ 36 ]. Macrophages are classified into two major subtypes: M1 (proinflammatory or classically activated) and M2 (anti-inflammatory or alternatively activated) [ 37 , 38 ]. In the lamina propria of inflamed gut, M1 macrophages break down the tight junction proteins, damage the epithelial barrier, and induce epithelial cell apoptosis, leading to excessive inflammation by secreting cytokines such as IL-12, IL-23, IL-1β, TNF-α, and ROS and ultimately causing tissue damage [ 37 , 38 , 39 , 40 ].…”

“…Macrophages are classified into two major subtypes: M1 (proinflammatory or classically activated) and M2 (anti-inflammatory or alternatively activated) [ 37 , 38 ]. In the lamina propria of inflamed gut, M1 macrophages break down the tight junction proteins, damage the epithelial barrier, and induce epithelial cell apoptosis, leading to excessive inflammation by secreting cytokines such as IL-12, IL-23, IL-1β, TNF-α, and ROS and ultimately causing tissue damage [ 37 , 38 , 39 , 40 ]. Conversely, M2 macrophages promote inflammation resolution and tissue remodeling by upregulated factors such as IL-4, IL-10, CD163, CD206, and Arg1 [ 37 , 38 , 39 , 40 ].…”

Pathophysiology of Inflammatory Bowel Disease: Innate Immune System

“…Curiously, CD-patient-derived macrophages show diminished HGF secretion, possibly affecting epithelial restoration in these patients [ 173 ]. Classically, two main polarized macrophage phenotypes have been proposed, pro-inflammatory M1 and anti-inflammatory M2 [ 174 ]. Tissue repairing M2-like macrophages promote stimulation of wingless-related integration site (WNT) signaling in response to differentiation driven by signal transducer and activator of transcription (STAT)-6 [ 175 ] through a mechanism dependent on the alarmin IL-33 [ 176 ].…”

Impact of the flame retardant 2,2’4,4’-tetrabromodiphenyl ether (PBDE-47) in THP-1 macrophage-like cell function via small extracellular vesicles

“…Accumulating evidence has shown that M1 and M2 macrophage polarization participates in several innate immune responses but also shapes the adaptive immune response (28). Macrophage-derived EVs have been described, showing that they play an important role in the pathogenesis of inflammatory exacerbation and resolution by interacting with different cell types (16,(29)(30)(31). A paradigmatic example of this is the crosstalk between tumoral and immune cells that secrete EVs in the tumor immune microenvironment, modulating immunological activities including macrophage polarization, T cell regulation, and the inhibition of natural killer (NK) cell activity (32,33).…”