ABSTRACT: To investigate the effect of emollient on atopic march in a murine model of chronic atopic dermatitis (AD). Mice were divided into 3 groups and treated with topical calcipotriol and ovalbumin alone or with a linoleic acid-ceramide-containing emollient. After 28 days, clinical, histological, and transcriptomic analyses were performed in skin lesions, lung and serum. Calcipotriol combined with ovalbumin induced a typical AD model with concomitant increased expression of Th2 and basophil-related genes in the lung. Compared to AD group, emollient group: 1) Skin: clinical severity and inflammatory cell infiltration were significantly reduced and transcriptomic analysis revealed significant downregulation of AD-related genes (286 of 1450 differentially expressed genes (DEGs)) including those related to innate inflammation (S100a8/a9, Il1b, Defb3/6, Mmp12), chemokines (Cxcl1/3, Ccl3/4) and barrier (Krt2/6b/80, Serpinb12, Lce3e, Sprr2). DEGs down-regulated by emollient were enriched in mitochondrial OXPHOS-related pathways, while up-regulated DEGs were mainly enriched in axon guidance, tight junctions, as shown by KEGG analyses. 2) Serum: total IgE and TSLP levels were significantly decreased, and IL-4 levels showed a decreasing tendency. 3) Lung: 187 of 275 upregulated DEGs were significantly downregulated in lung tissue including genes involved in cytokine and cytokine receptor interaction (Cxcl2/Cxcr2, Ccl2/3, Csf3r, etc.) and basophil activation (Mcpt8, Cd200r3, Ms4a2). Thus, topical emollient not only reduces skin inflammation and maintain skin barrier homeostasis by inhibiting the mitochondrial respiratory chain, but also limits systemic inflammation by decreasing TSLP and IgE levels. Moreover, it reduces respiratory chemokine production and basophil infiltration and activation, providing a molecular basis for blocking the atopic march.
