PPAR is a transcription factor that serves as a lipid sensor and that contributes to skin homeostasis. Because PPAR is down-regulated in the skin of atopic dermatitis patients, investigations into its functions might provide further understanding to disease pathogenesis. We studied the skin microbiome and the immune system of PPAR deficient mice and littermate controls. Moreover, we also determined the composition of epidermal eicosanoids, leukotrienes and prostaglandins. We found that, in the steady state, PPAR deficient mice exhibit a discreet alteration of epidermal barrier function with a moderate increased TEWL and a normal skin surface pH. PPAR deficiency alters the composition of skin microflora and leads to changes in innate and adaptive skin immune system. NOD2 pathway and expression of innate cytokines is triggered in the epidermis of PPAR deficient mice when compared to littermate controls. We observed an increased proportions of Langerhans cells associated with increased expression of IL23 and IL17A associated with increased production of IL-17A in epidermal gamma/delta T cells. Moreover, we determined higher amounts of 8-HETE and enhanced Alox8 expression associated with the enhanced expression of various differentiation markers for keratinocytes including FLG in the epidermis of PPARα deficient mice when compared to littermate controls. Thus, down-regulation of PPAR in atopic skin might contribute to modifications of skin microenvironment not only by impairing the skin immune system and altering the skin lipid composition, but also by modifying the skin microbiome.

PPAR-alpha deficiency drives altered bacterial skin colonization and abnormal eicosanoid skin composition.