Macrophage polarization: an effective approach to targeted therapy of inflammatory bowel disease

ABSTRACT

Introduction: Inflammatory bowel disease (IBD) is a systemic disease with immune abnormalities that can affect the entire digestive tract. A high percentage of patients with IBD are unresponsive to current pharmacological agents, hence the need exists for novel therapeutic approaches. There is compelling evidence that macrophage polarization plays a key role in the remission of IBD patients and that it could open up future treatment options for patients.

Areas covered: This paper highlights the crucial role of macrophage polarization in IBD. The authors shed light on the phenotype and function of macrophages and potential drug targets for polarization regulation. Existing approaches for regulating macrophage polarization are discussed and potential solutions for safety concerns are considered. We performed a literature search on the IBD and macrophage polarization mainly published in PubMed January 2010–July 2020.

Expert opinion: Evidence indicates that there are fewer M2 macrophages and a high proportion of M1 macrophages in the intestinal tissues of individuals who are non- responsive to treatment. Regulating macrophage polarization is a potential novel targeted option for IBD treatment. Improved mechanistic insights are required to uncover more precise and effective targets for skewing macrophages into a proper phenotype.

KEYWORDS:

• Inflammatory bowel disease
• macrophage polarization
• immune regulation
• targeted therapy

Article highlights

• A high percentage of patients with IBD are unresponsive to current pharmacological agents, hence the need exists for novel therapeutic approaches

• Intestinal macrophage polarization is involved in the development and treatment of IBD and associated with individual unresponsiveness.

• Skewing macrophage phenotype can exert a pivotal effect in the resolution of intestinal inflammation and mucosal healing.

• Targeting macrophage polarization holds great promise for the treatment of IBD.

• More mechanistic insight is necessary to define specific markers of macrophage phenotype and discover more potential targets.

This box summarizes key points contained in the article.

Acknowledgments

YY Du contributed significantly to complete manuscript preparation. L Rong and YH Cong contributed to the constructive discussions. B Wang, N Zhang and L Shen contributed to the conception of the review. All authors read and approved the paper.

Declaration 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 Program of Shanghai Committee of Science and Technology, China (Grant No. 17401902300).