Atopic Dermatitis (AD) is the most common chronic inflammatory skin disease, which is caused by an exaggerated T helper 2 cell-mediated immune responses and impairment of the skin barrier function. Single loss of function (LOF) mutations of filaggrin (FLG) are the strongest known genetic risk factor for AD. In Europeans an allele frequency of approximately 10% for a single LOF mutation of FLG can be found, but does not necessarily lead to AD-manifestation. FLG is essential for the skin barrier function. Mutations can thus lead to a disrupted skin barrier. It is known that atopic and healthy skin differ in bacterial diversity and that AD-skin is associated with dysbiosis. It is also known that healthy individuals with a single LOF mutation of FLG have a skin microbiota which is in part similar to that of AD patients. However, the mechanism through which the microbiota contributes in the pathogenesis of AD need further investigation and it is still unclear to what extent the AD microbiota is a driver of the disease. To investigate this question further, we stimulated 3D skin equivalents (3DSE) with collected microbiota of localization-, gender- and age-matched probands (AD- and healthy). Defined skin areas were rinsed with a saline/detergent solution to harvest the microbiota. Subsequently, the rinsing solution containing the microbiota was sequentially centrifuged to remove host mediators/cellular debris. The microbiota samples were then applied to the surface of 3DSE and the expression of skin differentiation markers like FLG were analyzed by real-time PCR. Our findings indicate that the treatment of the 3DSE with the AD-derived microbiota induce a decreased expression of FLG compared to 3DSE treated with the control-microbiota. These results support the hypothesis, that the AD-microbiota maintain the disrupted skin barrier and provide further evidence that the dysbiosis of the AD microbiota is linked to the manifestation/development and course of this skin disease.

ESDR138 - Expression of epidermal differentiation markers is modulated by AD-microbiota

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING