Systemic corticosteroid and autologous adipose-derived mesenchymal stromal cell therapy are associated with convergent miRNA–cytokine network profiles in severe equine asthma

MicroRNAs (miRNAs) regulate key inflammatory pathways in asthma. Severe equine asthma (SEA), a naturally occurring airway disease, shares important inflammatory features with certain phenotypes of human asthma and represents a valuable translational model. The objective of this study was to compare the effects of systemic corticosteroid therapy and autologous adipose-derived mesenchymal stromal cell (AD-MSC) therapy on bronchoalveolar lavage fluid (BALF) miRNA expression and cytokine networks in horses with SEA. Horses with exacerbated SEA were randomized to receive either systemic dexamethasone or intrabronchial AD‑MSCs in an active‑controlled study with blinded outcome assessment. BALF was collected at baseline (T0) and three weeks post‑treatment (T1) for miRNA sequencing and quantification of cytokine mRNA expression and protein concentrations. Associations were assessed using correlation‑based analyses with control for multiple testing. At T0, IL‑1β and IL‑8 showed the strongest associations with multiple miRNAs, including miR‑223, members of the miR‑129 family, and miR‑338‑5p. After treatment (T1), miRNA expression profiles and miRNA–cytokine association patterns were largely similar between the dexamethasone and AD‑MSC groups, with no statistically significant group‑level differences observed. Several miRNAs, including miR‑146b‑3p and miR‑532‑5p, demonstrated significant temporal changes between T0 and T1. Systemic corticosteroid therapy and intrabronchial AD‑MSC therapy were associated with broadly comparable miRNA–cytokine association patterns in SEA. The identified miRNA signatures overlap with pathways previously described in human asthma and support the translational relevance of SEA as a model for inflammatory airway disease. These findings provide a foundation for future functional studies and the exploration of miRNAs as candidate biomarkers.