Charcot-Leyden Crystals drive pathology and inflammation in muco-obstructive lung disease

Mucus plugging leading to airway obstruction is a hallmark of chronic respiratory diseases, yet the biology of plugs and their contribution to airway inflammation remain poorly defined. Through guided retrieval and analysis of plugs from patients with allergic bronchopulmonary aspergillosis, we identify Charcot-Leyden crystals that are formed from eosinophil-derived Galectin-10 as ubiquitous and mechanistic components that generate highly localized type 2 inflammatory niches. These niches exhibit mixed granulocytic infiltration, including neutrophil activation and extracellular trap formation that reinforces mucus tenacity. In a mouse model recapitulating these characteristics, plugs containing Charcot-Leyden crystals induced persistent obstruction and inflammation, whereas systemic administration of a crystal-dissolving anti-Galectin-10 antibody markedly reduced crystal burden, inflammation and airway plugging. We further establish Galectin-10 as a sensitive biomarker of acute disease and develop a positron emission tomography approach enabling noninvasive visualization of crystal-rich plugs. These findings position Galectin-10 as a central driver and tractable therapeutic target in muco-obstructive lung disease.