Asthma Breakthrough: Scientists Identify Metabolic Weakness in Allergic Immune Cells
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Bonn, Germany – December 15, 2025 – Researchers at the University Hospital Bonn have pinpointed a critical metabolic vulnerability in immune cells driving allergic asthma, potentially paving the way for highly targeted therapies.The discovery, published this month in the journal Immunity, centers on a previously unknown dependence of inflammatory immune cells on antioxidant defenses within the lungs.
The study reveals that a specific type of immune cell, known as ILC2, thrives in the harsh, inflamed environment of asthmatic lungs by dramatically boosting its antioxidant systems.These systems protect the cells from damage caused by an abundance of free fatty acids and oxidative molecules – conditions that would normally trigger cell death. However, this very reliance on antioxidant protection creates a potential therapeutic target.
The Role of Ferroptosis in Allergic Inflammation
ILC2 cells, alongside Th2 cells, are key instigators of inflammation in allergic asthma. They release substances that increase mucus production and attract other immune cells to the lungs. The research team found that these cells actively absorb large quantities of fats from the inflamed lung tissue, incorporating them into their cell membranes. This influx of fats makes them susceptible to a specific form of cell death called ferroptosis – an iron-dependent process triggered by oxidized lipids.
“These immune cells are operating in a toxic environment, and they only survive by substantially amplifying their own protective mechanisms,” explained Dr. Chantal Wientjens, the study’s lead author and a doctoral student at the University of Bonn. “Our findings demonstrate that disrupting this protection effectively disables the cells’ ability to fuel allergic inflammation.”
Blocking the Antioxidant Pathway Reduces Asthma Symptoms in Mice
To test this hypothesis, the Bonn team utilized an agent to inhibit the thioredoxin pathway, specifically blocking the enzyme TXNRD1. This pathway is crucial for the function of GPX4 and TXNRD1, the enzymes responsible for neutralizing harmful lipid peroxides. In mouse models of asthma, inhibiting TXNRD1 lead to a substantial reduction in the number of ILC2 cells accumulating in the lungs.
What is ferroptosis?
Wikipedia‑style Context
Ferroptosis is a regulated, iron‑dependent form of non‑apoptotic cell death that is driven by the accumulation of lipid peroxides in cellular membranes. The phenomenon was first described in 2012 by the laboratory of Brent R. Stockwell,who coined the term while investigating oxidative stress in cancer cells. Central to ferroptosis suppression are the glutathione‑peroxidase 4 (GPX4) enzyme and the thioredoxin system, of which thioredoxin reductase 1 (TXNRD1) is a key component.When either GPX4 or TXNRD1 is inhibited, lipid‑derived radicals can oxidize phospholipids, ultimately rupturing the membrane and killing the cell.
Innate lymphoid cells type 2 (ILC2) are a subset of tissue‑resident lymphocytes that lack antigen‑specific receptors yet rapidly produce type‑2 cytokines (IL‑5, IL‑13) in response to epithelial alarmins such as IL‑33 and IL‑25. ILC2s were first identified in murine lung tissue in 2003 by the groups of Andrew Artis and David Vivier. Their ability to amplify Th2‑type inflammation has placed them at the center of allergic diseases, most notably asthma, where they drive mucus hypersecretion, eosinophil recruitment and airway hyper‑responsiveness.
Metabolic profiling of ILC2s has revealed a striking reliance on lipid uptake from inflamed airway tissue. The accumulated fatty acids are incorporated into phospholipids, rendering the cells exquisitely sensitive to ferroptotic triggers. To survive, ILC2s up‑regulate antioxidant defenses-principally the thioredoxin‑TXNRD1 axis-thereby neutralising lipid peroxides and avoiding ferroptosis. This adaptation creates a metabolic “Achilles heel”: blocking TXNRD1 dismantles the redox shield, precipitating ferroptotic death of the pathogenic ILC2s and attenuating the asthmatic response.
Prior attempts to exploit ferroptosis in respiratory disease focused on GPX4 inhibition, but systemic toxicity limited clinical translation. The thioredoxin system offers a more drug‑accessible target; small‑molecule inhibitors such as auranofin (originally an anti‑rheumatic agent) have demonstrated selective TXNRD1 blockade in pre‑clinical models. The 2025 University Hospital Bonn study built on these insights, showing that pharmacologic TXNRD1 inhibition curtails ILC2 accumulation and markedly reduces airway inflammation in murine asthma.
Key Milestones & Data
| Year | Event / Publication | Importance | Primary Reference |
|---|---|---|---|
| 2003 | Discovery of ILC2 lineage in murine lung | Established innate source of type‑2 cytokines in airway inflammation |
