The role of IL-32 in type 1 dominant chronic inflammatory skin diseases

• Applicant: Professor Felix Lauffer, Ph.D.
• Subject Area: Dermatology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 572006072

The group of type 1 dominant inflammatory skin diseases is characterized by a non-infectious cytotoxic immune reaction against structural components of the skin (interface dermatitis). The prototype disease is lichen planus. Affected individuals suffer from stigmatizing skin lesions, pain and itching. To date, no targeted therapies are available for these diseases. In preliminary work, we have shown that in lichen planus a type 1 dominant immunity leads to inflammatory cell death of keratinocytes, which favors the maintenance of interface dermatitis. Based on comprehensive RNA sequencing of more than 500 skin biopsies of inflammatory skin diseases, we searched for novel markers of interface dermatitis. We identified IL-32 as a gene whose expression correlates significantly and exclusively with type 1 dominant skin diseases. To date, IL-32 has not been described or studied in this disease group. In addition, the biology of IL-32 is incompletely understood. Both pro- and anti-inflammatory effects of IL-32 have been described. Furthermore, it is still not known via which receptor or signaling pathway it exerts its effects. Since only the genome of higher developed mammals and not that of rodents encodes the IL-32 gene, we plan a comprehensive investigation of IL-32 in the human models of inflammatory skin diseases well established in our laboratory. The following objectives will be pursued: 1. to characterize the effects of IL-32 in the interaction between resident (keratinocytes, fibroblasts) and infiltrating cells (T cells) in lichen planus. 2. to investigate the signaling pathway of IL-32 by knocking out potential downstream proteins and integrins in human keratinocytes. 3. to analyze the effects of IL-32 on metabolic activity and regulated cell death of skin and immune cells. 4. to assess the therapeutic potential of IL-32 blockade in lichen planus. All investigations are carried out on primary human cells or skin biopsies from affected individuals, which is a significant difference to previous studies on IL-32, which were mainly carried out on cell lines. The knowledge gained in this research project will help to understand both the general biology of IL-32 and its function in the context of type 1 dominant skin diseases. The translational goal of this research project is also to expand the previously inadequate therapeutic options for this disease group and thus improve the quality of life of affected individuals.

• DFG Programme: Research Grants