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Orchestrating inflammation: non-coding RNAs as master regulators of macrophage function in chronic obstructive

Xinyu Yong^1,2, Xian Luo^1,2, Xiaobing Chen^1,2

¹Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.

Frontiers in Immunology

|November 13, 2025

Summary

Non-coding RNAs (ncRNAs) critically regulate macrophage function in chronic obstructive pulmonary disease (COPD). Targeting these ncRNA-macrophage interactions offers promising avenues for personalized COPD diagnostics and therapies.

Area of Science:

Immunology
Molecular Biology
Pulmonary Medicine

Background:

Chronic obstructive pulmonary disease (COPD) is a significant global health issue.
Macrophage dysfunction and chronic inflammation are hallmarks of COPD.
Non-coding RNAs (ncRNAs) are increasingly recognized for their role in regulating macrophage behavior.

Purpose of the Study:

To review the current evidence on how ncRNA-macrophage regulatory axes contribute to COPD pathogenesis.
To explore the diagnostic and therapeutic potential of ncRNAs in COPD.
To identify challenges and future directions in ncRNA-based COPD research.

Main Methods:

Comprehensive literature review of studies investigating ncRNAs (miRNAs, lncRNAs, circRNAs) and their impact on macrophage polarization in COPD.
Analysis of molecular pathways (e.g., NF-κB, STAT3) involved in ncRNA-mediated inflammation.
Examination of clinical studies translating mechanistic insights into biomarkers and therapeutic targets.

Main Results:

Pro-inflammatory miRNAs (e.g., miR-155) drive M1 macrophage polarization and inflammation.
Anti-inflammatory miRNAs promote resolution of inflammation.
Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) employ complex regulatory mechanisms, including acting as scaffolds and competing for microRNAs.
ncRNAs have shown potential as diagnostic biomarkers and therapeutic targets in human COPD patients.

Conclusions:

ncRNA-macrophage regulatory axes are key drivers of COPD progression.
Targeting these axes presents a promising strategy for developing novel diagnostics and therapeutics for COPD.
Further research is needed to overcome methodological challenges and fully realize the clinical potential of ncRNA-based precision medicine in COPD management.

Keywords:

biomarkers chronic obstructive pulmonary disease inflammation macrophages non-coding RNAs

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