CD Laboratory for Chronic Inflammatory Skin Diseases

This CD Laboratory is investigating the molecular mechanisms underlying chronic inflammatory skin diseases and how these change under specific treatments. The aim is to identify new therapeutic approaches and biomarkers for treatment response.

Chronic inflammation is classified by the World Health Organization as one of the greatest threats to human health. Chronic inflammatory skin diseases, such as psoriasis, are responsible for a high disease burden due to the frequent stigmatisation and can affect organs other than the skin. Psoriasis can also affect peripheral joints (psoriatic arthritis) or vertebral bodies (spondylitis psoriatica).

Despite major advances in targeted therapies, the role of key cells in cutaneous inflammation is not yet fully understood. A better understanding of cellular and molecular pathomechanisms and their modification by treatment will help to find new approaches for long-term improvement of chronic skin inflammation.

This CD Laboratory is investigating how tissue-resident memory T cells (TRM) of the skin and subcutaneous adipose tissue respond to a specific biological treatment in psoriasis, a model disease for chronic inflammation. To do this, cellular and molecular networks in different tissue compartments are analysed over time. These skin tissue compartments include the epidermis, the dermis, the subcutaneous adipose tissue, and the hair follicular region.

The project is divided into three work packages, which test the presence, position and molecular signature of pathological TRM in chronic inflammation in the skin and subcutaneous adipose tissue, its accessibility for targeted therapy and its contribution to disease chronicity in psoriasis.

In the first work package, patients with psoriasis will be recruited, treated with an IL-23-p19 inhibitor and sequential skin biopsies (including subcutaneous fat) will be taken before and during therapy. In the second work package, state-of-the-art systems biology approaches will be applied, including single-cell and spatial RNA sequencing, to map the inflammatory signature and interactome to individual cells in the epidermis, dermis and subcutaneous adipose tissue. The third work package includes a systems immunology approach, complemented by innovative in vitro assays, to characterise the exact contribution of antigen-presenting cells, structural cells and Th17 cells (including TRMs) from different compartments to disease mechanisms and their response to IL-23-p19.

The following specific results are aimed to be achieved with the project: i) identification of TRM from adipose tissue as a factor in chronic skin inflammation, ii) presentation of molecular targets of pathogenic T cells as new therapeutic approaches and iii) characterisation of potential molecular patterns as biomarkers for response to treatment, which can then be specifically tested in future studies.