Rationale: IL-33 and IL-1RL1 are vital asthma genes. Basal cells in airway epithelium express IL-331, while expression of its receptor IL-1RL1 is relatively low in airway epithelial cells. Overexpression of IL-33 in human bronchial epithelial cells leads to reduced cell viability2,, but the effects of exogenous IL-33 on the airway epithelium remain unknown. We aimed to characterize the IL-33-driven transcriptomic changes in primary bronchial epithelial cells (PBECs) cultured as 3D organoid or as air-liquid interface (ALI) cultures, stratified for disease state.

Methods:

Results: Stimulation of PBECs differentiated in ALI cultures with recombinant IL-33 in-vitro does not induce any significant changes in gene expression after multiple testing correction. By testing if there's any effect of IL-33, we notice slight increase in the gene expression based on increasing levels of IL-33, however this is undetectable by the threshold for significantly differentiated genes. In addition, PBECs grown in 3D epithelial organoids do not show any changes in gene expression after IL-33 stimulation, irrespective of concentration and disease state.

Conclusions: There is no significant transcriptional signature of IL-33 in epithelial cells, irrespective of the culture system. We suggest to study other effector cells such as ILC2 or mast cells for the effect of IL-33.