PI: Dott.ssa Emanuela Camera.

The proposed study addresses lipidomics and metabolomics in plasma and non-invasive samples of skin surface lipids, i.e., sebum and intercellular matrix in the permeability barrier, in association with cytokine profiling, skin biophysics, and clinical data to delineate informative and comprehensive diagnostic approaches to be applied to the characterization of individual metabotypes of psoriasis, psoriatic arthritis (PsA), and atopic dermatitis (AD). Cytokines play a crucial role in the pathogenesis of psoriasis, PsA and AD, as they mediate immune responses and inflammatory processes in the skin and joints. High throughput analyses, data mining, 3D-skin models, and methods for pattern discovery will be exploited to design innovative strategies to identify biosignatures of the driving cytokine signals in easy to access skin biomatrices.

Project duration: 24 months

Psoriasis and atopic dermatitis (AD) are immune-mediated chronic inflammatory skin disorders (CISD) characterized by the disequilibrium of cytokines, with the prevalence of one or more mediators. CISD are not confined to the skin. AD is frequently associated with elevated IgE levels and overt allergies or asthma, and psoriatic arthritis (PsA) develops in ~30% of people with psoriasis. However, the available therapies have several black box warnings, due to the increased risk for serious collateral diseases. CISD have variable clinical manifestations. Their molecular pathogenesis can be divided into an initiation and maintenance phase. General metabolic dysregulation underlies both psoriasis and AD, despite the apparently different spectrum of these dermatoses and may further unfavourably impact the quality of life. The type of psoriasis or AD, the severity grade, comorbidities, and patients' profiles should be taken into accounts when selecting the treatment. Comprehensive diagnostic procedures are needed to better characterize patients and guide personalization of the therapy.

We expect to find distinctive patterns of plasma and skin surface lipidomics/metabolomics associated with peripheral and skin surface cytokine profiles and cellular functional phenotype. For the first time, this study investigates the lipid composition of plasma, sebum, SC and skin barrier properties in association with cytokine signalling and expands the current knowledge on the associations between circulating and skinborne lipid metabolisms, both in patients with CISD and healthy controls. We expect to prove the influence of cytokine signals on pathways involved in the elaboration of sebum and epidermal lipids in the SC.