Airway epithelial type-2 alarmin profiles: Blood eosinophil counts remain in memory.

Epithelial cytokines are involved in the orchestration of T1/T2 inflammatory patterns. We question the persistence of this trait in air-liquid interface epithelial cultures (ALI) and whether this local orientation can be related to systemic patterns (e.g. blood eosinophil counts (BECs). We investigated alarmin release related to high-vs-low T2 phenotypes associated with chronic airway diseases. ALIs were reconstituted from 32 control, 40 chronic obstructive pulmonary disease (COPD) and 20 asthmatic patients. Interleukin-8 (IL-8; a T1-cytokine), IL-25, IL-33 and Thymic Stromal Lymphopoietin (TSLP)(T2-alarmins) concentrations were assessed in subnatants at steady state, and used to explain blood neutrophil and eosinophil counts. IL-25 and IL-8 levels were highest in asthma ALI-subnatants, whereas IL-33 was sparsely detected. TSLP levels were similar among groups. All asthma cell cultures were T1-high/T2-high, while COPD and controls tended to be mixed. BECs were independently explained by both disease and in-culture T2-alarmin levels, irrespective of the T2-alarmin considered. The epithelial ALI-T2 signature was more frequently high in patients with a BEC>300/mm 3 . Despite removal from an in vivo environment for ≥2 months, ALIs release disease-specific cytokine "cocktails" into their subnatants, suggesting continued persistence of alarmin orientation in differentiated cell-line environments. This article is protected by copyright. All rights reserved.