(A) Objectives: The strategic workshop set up by the “excellence” working groups of SZTE, DE and SZBK (in close cooperation with the SE’s excellent researchers) aims to explore how intercellular communication of the cells that create the interfaces participates in the most frequent immunological and inflammatory diseases of the human skin and intestinal tract. Introduction The main task of human body interfaces (barriers) is to establish the first line of defence against environmental stimuli. The main target of this project is the 2 most extensive barrier, skin and intestinal tract testing. The justification and necessity of the topic is shown by the fact that barrier defects of these organs are associated with the highest frequency of human diseases such as acne vulgaris, psoriasis, atopic dermatitis, coeliac disease, Crohn’s disease and ulcerative colitis, combined with inflammatory bowel disease (IBD). Although significant, but still only partial, efforts have been made to uncover patho-mechanisms, it is clear that the treatment of these pathologies is far from being resolved — so diseases affect the quality of life of hundreds of millions of people worldwide. There has been a significant paradigm shift in the functioning of barriers in recent years; the argument that barriers perform only passive ‘physicochemical isolation’ functions has been rejected. There is now more and more evidence that barrier is a complex, dynamically variable, ‘active’ functional system, the main components of which are coordinated immunological and (micro)biological mechanisms (in addition to physical protection) that react to, but protect against, the harmful effects of environmental hazards (stressors). The immunological barrier is maintained by the own immune system of the skin and gut, which contains cellular and humoral components of congenital and acquired immunity. The microbiological barrier, which has recently become the center of attention, is created as an interplay between the huge microbiota present on the interfaces and the barrier cells that amplify each other’s influences, constantly ‘teaching and forming’ each other. Thanks to recent (including own) research, it has also emerged that a multidimensional intercellular communication network of barrier cells and microbiota components is the cornerstone of physiological/homeostatic functioning of barrier functions. In theory, communication can take place in 3 ways: using direct physical contact of cells and the messenger function of various (ii) humoral mediators and (iii) partiicular elements (extracellular vesicles, e.g. exosomas). The common feature of the above diseases is a variable degree, often chronic inflammation; dysregulation of the complex immune response to stressors; barrier defect; and the cumulative consequences of these. However, it is not clear which of these inseparable mechanisms are the causes and the consequences. Previously, immunohomeostasis rollovers (e.g. autoimmune activation) and abnormal intensification of inflammation (such as “physiological clearance”) lead to the development of diseases (so-called in-out theories). However, recent experimental data suggest that the primary defect of barrier (e.g. through mutations) can act as a ‘trigger’. According to this view, the defect disrupts the homeostasis of the barrier described above, which, on the one hand, cannot prevent the effects of stressors and, on the other hand, allows the invasion of certain components of the symbiotic microbiota (so-called outside-in theory). In view of the above, the Workshop intends to implement the molecular medicine R & D programme along the following working hypothesis: In our opinion, the pathological alteration of complex barrier functions in the above-mentioned immunological and inflammatory diseases is due to the loss of the homeostatic function of intercellular communication, thus triggering a chain of pathological responses, leading to the defect of the barrier and the development of the disease. (B) The aim of the programme is to apply a multidisciplinary, system-based, multi-level experimental matrix along the tasks (F) and working stages (M) defined by the Workshop. F1. Examination of in vitro cell systems The main goal of F1 as the backbone of the project is to map the impactor’s responses to various stressors and intercellular communication “patterns” of the barrier cells at individual cell level under physiological and pathological conditions. F1/M1. Development of cell cultures and co-cultures In the first half of M1 (supplementing cell cultures routinely used by working groups) human cell systems are optimised, producing the following (primary cultures, cell lines, genetically modified cell systems): —Specific human cell cultures o Primer cells: epithelial cells (e.g. keratinocytes); mesenchimal cells (e.g. fibroblasts, smooth muscle cells); MIR