Allergic diseases often occur within the framework of the so-called. ‘allergic march’ – the significant role of atopic dermatitis (AZS) as a trigger for asthma and inflammation in remote tissues has been proven. In our research, we identified the important role of abnormal communication between the skin and the immune system in AZS - mediated by small extracellular vesicles (sEV), produced by diseased keratinocytes, aggravating the chronic allergic state in the skin. Since sEVs are carried in the body along with circulation, we suspect their involvement in promoting allergic inflammation outside the skin and, consequently, in the progression of allergic walking and asthma induction. Since we have previously identified global changes in the pathways involved in lipid synthesis and elongation as the underlying mechanism for follicular remodeling, resulting in the induction of pro-allergic responses, the project will start by generating a panel of cell lines with overexpression and inactivation (CRISPR knock-out) of the genes encoding them and defining the effect of specific enzymes on sEV-mediated antigen-specific responses of CD1a-dependent T cells. Then, due to the multi-systemic course of the ‘allergic march’, we will use in vivo studies on humanised transgenic mice demonstrating the experation of the human CD1a molecule (CD1a-Tg). CD1a-Tg mice were generated and tested in the laboratory of our scientific partner at the University of Oxford. Thanks to this, we will determine the effect of altered follicles produced in AZS by human keratinocytes with reduced expression of the epidermal protein philagrine on the course of dust mites-induced domestic allergic pneumonia. In the last phase of the project, we will test the therapeutic potential of follicles with a precisely planned lipid profile, secreted by genetically modified cells, as a strategy modifying the course of asthma development in vivo.