Group Leader: Lajos Kemény
In his HCEMM project (entitled as “The role of keratinocytes in healthy innate immune memory and in the chronic skin disease psoriasis”), his senior group investigates one of the most prevalent human skin diseases, psoriasis. His group has previously showed that epidermal keratinocytes of non-lesional, healthy-looking skin of psoriatic patients exhibit an increased sensitivity to inflammatory signals, and this plays a crucial role in the development of psoriatic skin lesions. They also suggested that exposure of the skin to microbial and/or danger signals results in molecular changes in cells, that similar to immune memory, in healthy skin is beneficial for the tissue, resulting in better skin barrier formation; however, in chronic inflammatory diseases, such as in psoriasis this mechanism contributes to the pathology. Bases on these assumptions, his group aims to identify the basic mechanism in keratinocytes to environmental signals to establish the role of local tissue memory to danger signals in skin physiology and in psoriasis. The local tissue memory to proinflammatory signals will be investigated at the tissue and cellular level, and generated data will be used for drug repurposing. At the tissue level, skin biopsies from healthy individuals and from psoriatic patients will be taken, and immunohistochemistry, transcriptomics and epigenetic modifications of the samples will be compared. For cross-talks between keratinocytes, fibroblast, lymphocytes, and mesenchymal stem cells, different co-cultures will be studied, and the proliferation and cytokine production will be measured. At the cellular level, cultured healthy and psoriatic keratinocytes, and human induced pluripotent stem cell-derived psoriatic keratinocytes will be used for comparison. With these investigations, they intend to gain knowledge about normal skin homeostasis, and also to initiate new strategies to control psoriasis and other chronic inflammatory skin diseases.