Macrophages-microenvironment crosstalk in fibrostenotic inflammatory bowel disease: from basic mechanisms to clinical applications

ABSTRACT

Introduction

Intestinal fibrosis is a common complication of Inflammatory Bowel Disease (IBD) with no available drugs. The current therapeutic principle is surgical intervention as the core. Intestinal macrophages contribute to both the progression of inflammation and fibrosis. Understanding the role of macrophages in the intestinal microenvironment could bring new hope for fibrosis prevention or even reversal.

Areas covered

This article reviewed the most relevant reports on macrophage in the field of intestinal fibrosis. The authors discussed current opinions about how intestinal macrophages function and interact with surrounding mediators during inflammation resolution and fibrostenotic IBD. Based on biological mechanisms findings, authors summarized related clinical trial outcomes.

Expert opinion

The plasticity of intestinal macrophages allows them to undergo dramatic alterations in their phenotypes or functions when exposed to gastrointestinal environmental stimuli. They exhibit distinct metabolic characteristics, secrete various cytokines, express unique surface markers, and transmit different signals. Nevertheless, the specific mechanism through which the intestinal macrophages contribute to intestinal fibrosis remains unclear. It should further elucidate a novel therapeutic approach by targeting macrophages, especially distinct mechanisms in specific subgroups of macrophages involved in the progression of fibrogenesis in IBD.

KEYWORDS:

• Macrophage
• repair
• inflammatory bowel disease
• fibrosis
• immunity

Article highlights

• Lots of pro-inflammatory cytokines exhibit pro-fibrotic effects in IBD.

• Local metabolic substrate and resident microbes regulate the metabolic modes of macrophages and determine their pro-fibrotic phenotypes.

• Specific intestinal microbes modulate macrophage polarization or function by bacterial fermentation products during fibrosis progression.

• Resident macrophages sense and respond to changes in physical (rigid matrix) or chemical (pH value) cues in the microenvironment.

• Intestinal macrophages collaborate with other types of surrounding cell through various cytokines, adhesion proteins and other mediators in the environment to jointly promote the formation of intestinal strictures.

• Muscularization induced by the abdominal activation of the ‘inflammation-smooth muscle hyperplasia axis’ may be the main cause of the stricture development.

• Large-scale GWAS is required to identify SNPs in fibrostenotic IBD patients.

This box summarizes key points contained in the article.

Acknowledgement

All figures were created by BioRender.com, and we thank Yifan Bao for helping us polish the figures.

Declarations of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work is funded by National Natural Science Foundation of China (82072223).