LSC - 2019 - The skin microbiome drives immune maturation and exacerbation of both skin and airway inflammation

Skin allergen sensitization can induce atopic dermatitis (AD), which is considered the starting point of the ‘atopic march’. The ‘atopic march’ is the progression of AD in infancy to allergic rhinitis and allergic asthma in childhood. We hypothesize that the skin microbiome drives immune maturation, and that the maturation state at the time of skin allergen sensitization determines the allergic airway inflammation phenotype following allergen challenge. Neonatal and adult mice were subjected to a 3-week epicutaneous allergen sensitization protocol followed by intranasal allergen challenges. Skin and lung tissue inflammation was assessed using histological and FACS analysis. Skin transcriptome and microbiome was analyzed using RNA-seq and 16S rRNA sequencing. The immune maturation state at the time of first sensitization determines a Th2 vs. a mixed Th2/Th17 driven allergic inflammation in both the skin and the lung. Naive neonatal mouse skin exhibited decreased antigen presenting cell frequencies and a decreased antigen uptake and processing capacity compared to adults. Transcriptome analysis revealed that genes associated with immune response and bacterial response pathways were enriched in adult skin compared to neonatal skin. Similar genes were downregulated in adult germ-free mouse skin, suggesting an important role for the microbiome. Epicutaneous allergen sensitization in adult mice was characterized by increased Staphylococcus aureus abundance on the skin, and neutrophil accumulation and increased IL17 gene expression in both the skin and the lung. Taken together, the skin microbiome drives immune maturation and exacerbation of both skin and airway inflammation.