Macrophage Polarization in Allergic Airway Inflammation

Macrophages in the lung exhibit remarkable plasticity, adopting pro-inflammatory (M1) or anti-inflammatory/tissue-remodelling (M2) phenotypes in response to environmental and cytokine cues. In allergic airway inflammation, M2-polarised macrophages driven by interleukin-4 and interleukin-13 foster eosinophil recruitment, mucus hypersecretion and airway remodelling, whereas M1-polarised cells driven by interferon-γ and microbial products contribute to neutrophilic inflammation and tissue damage. Dynamic shifts between these states underpin the initiation, progression and resolution of asthma. Key signalling pathways—including STAT3, STAT6, PI3K/Akt and PPARγ—integrate cytokine, metabolic and epigenetic inputs to determine macrophage fate. Cross-talk between airway epithelial cells, dendritic cells and recruited monocytes further refines macrophage function, influencing allergen sensitivity and steroid responsiveness. Understanding the balance of M1 versus M2 programming reveals novel targets for precision therapies aimed at restoring homeostasis, reducing exacerbations and improving long-term outcomes in asthma and related allergic airway diseases.

Research from Nature Portfolio

Recent studies have dissected the dual role of alternatively activated (M2 or YM1+) macrophages in allergic lung inflammation. Inhibition of M2 polarisation during disease induction diminished eosinophilic inflammation and airway remodelling but unexpectedly exacerbated neutrophil-driven pathology and airway hyperresponsiveness. When M2 inhibition was applied after inflammation was established, collagen deposition and eosinophilia were likewise reduced, yet a shift to neutrophilic infiltration persisted. These findings demonstrate that M2 macrophages support both tissue remodelling and protective regulation of neutrophilic responses, highlighting the need to target macrophage subtypes with temporal precision to avoid unintended exacerbation of airway hyperreactivity.

Macrophage Polarization in Allergic Airway Inflammation publication trend

The graph below shows the total number of articles in macrophage polarization in allergic airway inflammation across all publications each year (not limited to Nature Index journals).

Technical terms

Macrophage polarization: The process by which macrophages adopt distinct functional states (M1 or M2) in response to microenvironmental signals.

M1 macrophages: Classically activated macrophages induced by interferon-γ and microbial ligands, associated with pro-inflammatory cytokine production and microbicidal activity.

M2 macrophages: Alternatively activated macrophages induced by interleukin-4 and interleukin-13, involved in tissue repair, remodelling and modulation of allergic inflammation.

Signal transducer and activator of transcription 3 (STAT3): A transcription factor activated by cytokines and growth factors, critical for promoting M2 gene expression.

Peroxisome proliferator-activated receptor gamma (PPARγ): A nuclear receptor that regulates lipid metabolism and supports M2 polarisation in macrophages.

References

1. The HDAC10 instructs macrophage M2 program via deacetylation of STAT3 and promotes allergic airway inflammation. Theranostics (2023).
2. Dual role of YM1+ M2 macrophages in allergic lung inflammation. Scientific Reports (2018).
3. Nuclear receptor corepressor 1 deficiency exacerbates asthma by modulating macrophage polarization. Cell Death Discovery (2023).
4. Modeling the Effects of Cypermethrin Toxicity on Ovalbumin-Induced Allergic Pneumonitis Rats: Macrophage Phenotype Differentiation and p38/STAT6 Signaling Are Candidate Targets of Pirfenidone Treatment. Cells (2023).