Interleukin 17A in the fibrotic-related processes in endometrosis in the mare.

Abstract: Equine endometrosis is a chronic degenerative condition with fibrosis being one of the most significant characteristics. A growing body of evidence indicates the critical role of interleukin (IL)-17 in fibrotic disorders. However, its exact role during equine endometrosis remains to be discovered and explained. The main aim of the current study was to establish the expression of IL-17A signaling components in equine endometria with and without endometrosis as well as the effects of IL-17A on the transcriptomic signature, cellular functional characteristics, expression of extracellular matrix (ECM)-associated factors and components of prostaglandin (PGs) signaling in fibroblasts derived from endometrium with and without endometrosis. Protein abundance of IL-17 receptor subunit A was up-regulated in endometrium with endometrosis compared to the endometrium without endometrosis. RNA-sequencing results revealed that genes with IL-17A-affected expression in fibroblasts derived from endometrium without endometrosis are involved in e.g., monocyte chemotaxis and macrophage activation, while those with IL-17A-affected expression in fibroblasts derived from endometrium with endometrosis are involved in e.g., neutrophil activation and migration. Moreover, it was found that IL-17A affected the expression and activity of MMPs and TIMPs in the equine endometrial fibroblasts derived from both types of endometrium. Interleukin 17A affects the immunomodulatory properties of equine endometrial fibroblasts and the balance between ECM deposition and degradation depending on the origin of fibroblasts - whether derived from endometrium with and without endometrosis.