MAARS

Microbes in Allergy and Autoimmunity Related to the Skin

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 Obiettivo del progetto (Objective)

'Allergy and autoimmunity cause increasing burden to societies worldwide. We study the effect of microbiome on the skin, the forefront barrier to environment, on autoimmunity and allergy, using atopic dermatitis (AD) and psoriasis (PSO) as paradigmatic examples. We have detailed information about the genetic risk factors, as well as the molecular and cellular players in AD and PSO, but we know very little how microbe-host interaction triggers and regulate inflammatory cascade leading to allergic or autoimmune reaction. We propose that environmental and genetic factors, characteristic to particular disease, initiate a cascade of inflammatory events through the modulation of anti-microbial defence. The dysregulation of innate as well as adaptive immune responses leads to inappropriate responses to physical, microbial or allergen challenge, finally manifesting in the clinical symptoms of AD or PSO. We propose to use high-throughput whole microbiome and transcriptomics analysis with bioinformatics and systems biology to unravel the pathways during the host-pathogen interactions which may trigger an allergic or autoimmune reaction. We will identify key microbes and molecular targets to develop novel intervention strategies to decrease and prevent the burden of allergy and autoimmunity.'

Introduzione (Teaser)

By obtaining mechanistic insights into the early processes underlying chronic inflammation, European scientists wish to understand the onset and progression of allergic or autoimmune diseases. Information generated will form the basis for the development of preventive or treatment measures for atopic dermatitis (AD) and psoriasis (PSO).

Descrizione progetto (Article)

Our immune system has evolved to attack foreign pathogens while at the same time recognising self-antigens. However, inadequate immune responses could lead to the development of allergic reactions or autoimmunity. Accumulating evidence indicates that microbial infections and dysbiosis (microbial imbalance) are critical determinants of the emergence of allergy or autoimmunity.

To unravel inflammatory pathways of host-pathogen interactions that may trigger allergic or autoimmune inflammation, scientists of the EU-funded 'Microbes in allergy and autoimmunity related to the skin' (MAARS) project have chosen to study AD and PSO as paradigm diseases. For this purpose, MAARS researchers are collecting 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 (HTS) of 16S ribosomal RNA is being used as a means for identifying the different bacteria species present in these samples. Partners are also analysing the microbe-regulated pathways in AD and PSO by DNA microarrays with data from 90 samples currently being annotated.

Work towards the immune aspect of AD and PSO includes the investigation of pathogen-derived triggering mechanisms resulting in the initiation of allergic or autoimmune skin reactions. This entails analysis of the impact of the microbial environment on dendritic cell functions as well as the role of T cell cytokines.

Preliminary experiments in an animal model of AD show that the dermal microbiome is central to the type of elicited T cell responses that determine the onset of allergy. In a similar way, the establishment of psoriasis models will aid in unveiling the importance of bacteria in the development of autoimmunity.

The translational component of the project involves 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.

Taken together, MAARS project activities will link 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, the study outcomes will contribute towards the alleviation of these and other allergic or autoimmune diseases.