338 Extracellular matrix (ECM) remodeling in atopic dermatitis (AD) as a putative contributor to the atopic march

Patients with AD are predisposed to developing other atopic diseases such as allergic asthma, a process known as the atopic march. The pathomechanism as to how skin communicates inflammation to the lungs remains largely elusive. We studied if and how inter-epithelial crosstalk between skin and lung may contribute to the atopic march using bioengineered atopic-like skin disease and bronchial epithelial models. Co-cultivation of the tissue models triggered an asthma-like phenotype in the bronchial epithelial models characterized by epithelial hyperproliferation, hyperplasia of mucus producing cells and upregulation of asthma markers. A targeted secretome analysis revealed the ECM-associated factors thromospondin-1, CD44, fibronectin and syndecan-4 as potentially relevant skin-derived mediators. SEM analysis of healthy and atopic ECM demonstrated distinct ECM disorganization and significantly reduced collagen (p≤0.001) and elastin (p≤0.01) concentrations. Transcriptomic and proteomic profiling of atopic fibroblast-derived ECM revealed distinct ECM-remodeling pathways involved and significant upregulation of proteins associated with ECM-remodeling and inflammation including HTRA1, DDR2, and STAT1 (each p≤0.01). Ongoing studies aim to identify the causative mechanisms for the observed changes in the ECM produced by atopic fibroblasts, which could be rooted in inflammatory processes or fibroblast-keratinocyte crosstalk. In conclusion, the ECM produced by atopic fibroblasts is disturbed in structure and composition with increased ECM-remodeling, which may contribute to the progression of atopic diseases to other epithelia.