# Immunometabolic programming of macrophages in asthma pathogenesis and therapy

## TL;DR

This paper explores how macrophage metabolism influences asthma inflammation and how targeting these processes could lead to new therapies.

## Contribution

The paper provides a comprehensive review of macrophage immunometabolic programming in asthma and its therapeutic implications.

## Key findings

- Macrophage subsets in asthma adopt distinct metabolic states that drive different inflammatory phenotypes.
- Modulating macrophage metabolism can reduce airway hyperresponsiveness and structural remodeling in preclinical models.
- Macrophage metabolic reprogramming is a promising target for asthma therapy.

## Abstract

Asthma is a heterogeneous chronic airway disease in which immune dysregulation and metabolic imbalance jointly shape inflammatory phenotypes and clinical outcomes. Growing evidence identifies pulmonary macrophages as central integrators of inflammatory cues and metabolic programs, linking acute exacerbations with long-term airway remodeling. Distinct tissue-resident and monocyte-derived macrophage subsets polarize along an M1–M2 spectrum and adopt glycolysis-dominated pro-inflammatory states or fatty acid oxidation-centered reparative states that differentially drive neutrophilic versus type 2-biased eosinophilic inflammation. Rewiring of arachidonic acid–derived eicosanoid synthesis and cholesterol handling further tailors macrophage effector functions and modulates responsiveness to glucocorticoids. Preclinical studies demonstrate that pharmacological manipulation of macrophage glucose and lipid metabolism can attenuate airway hyperresponsiveness and structural remodeling, highlighting immunometabolic circuits as promising therapeutic targets in asthma. This review summarizes current advances in macrophage ontogeny, polarization and metabolic reprogramming in the asthmatic lung. It also discusses how these insights may inform metabolism-focused, macrophage-directed interventions.