Inadequate immune responses can lead to the development of allergic reactions or autoimmunity. Accumulating evidence also indicates that microbial infections and dysbiosis (microbial imbalance) are critical determinants of the emergence of allergy or autoimmunity. Scientists of the EU-funded MAARS (Microbes in allergy and autoimmunity related to the skin) project studied atopic dermatitis (AD) as a model for allergy and psoriasis (PSO), for autoimmune disease. The researchers collected patient skin samples (swab and biopsies) to make sense of the role of the skin microbiome in the pathogenesis of these diseases. State-of-the-art high-throughput sequencing of 16S ribosomal RNA identified the different bacteria, fungi and viruses in these samples. Partners also analysed the microbe-regulated pathways in AD and PSO by DNA microarrays using data from 90 samples. Work towards the immune aspect of AD and PSO included the investigation of pathogen-derived triggering mechanisms resulting in the initiation of allergic or autoimmune skin reactions. This entailed analysis of the impact of the microbial environment on dendritic cell functions as well as the role of T cell cytokines. Results showed for example that Lactobacilli produce short chain fatty acids including butyrate. Sodium butyrate downregulates activation of T cells and differentially regulates PSO-related chemokines in dendritic cells. Data indicated that Corynebacterium species are pro-inflammatory in PSO whereas the Lactobacillus species may have an anti-inflammatory role in both diseases. Moreover, C. simulans may contribute to the generation of autoantigens in PSO. The fungus Malassezia induces expression of pro-inflammatory cytokines and drives the expression of pro-inflammatory genes. The translational component of the project involved the selection of a series of membrane and secreted proteins as targets for the production of antibodies. Following validation, some of these targets could form the basis for the future design of vaccines. MAARS project activities have linked transcriptomics, microbiomics and genetics to provide a multi-parameter analysis of allergy and autoimmunity. Given the epidemic proportions of AD and PSO, and their significant health care costs – PSO medication globally costs $ 3.5 billion per year – the study outcomes will contribute towards the alleviation of these and perhaps other allergic or autoimmune diseases.
Skin, microbes, allergy, autoimmunity, inflammation, dermatitis, psoriasis