The aryl hydrocarbon receptor integrates signals from the commensal yeast Malassezia to attenuate inflammation in the atopic skin
Grantee: Salomé LeibundGut-Landmann, Professor, University of Zurich
Amount: DKK 4,199,654
Grant category: Research Grants in open competition
Year: 2022
Geography: Switzerland
With this project, Salomé LeibundGut-Landmann along with collaborator Giuseppe Ianiri aims to investigate the importance of aryl hydrocarbon receptor (AhR) activation in relation to treatment of allergic skin reactions, including atopic dermatitis.
AhR is a so-called transcription factor, activated by cyclic (aromatic) compounds, which regulates cellular signaling. It is known that AhR is important for maintaining the skin barrier and a healthy cutaneous immune system and Salomé and her team propose that this, at least in part, is regulated by the release of such aromatic compounds by the commensal (non-pathogenic) and very common skin fungal class, Malassezia.
Using both human keratinocytes and mouse models, this hypothesis will be tested and the biosynthetic pathways of aromatic binding partners (ligands) for Ahr produced by Malassezia strains will be characterized.
If successful, the understanding of the interplay between commensal fungi as part of the skin microbiome and cellular maintenance of the skin barrier could provide novel approaches for treating allergic reactions and other skin inflammatory conditions, like atopic dermatitis.
Investigating the regulation of Interleukin-36 cytokine activity in the pathogenesis of generalised pustular psoriasis
Grantee: Mark Mellett, Group Leader, University Hospital Zürich
Amount: DKK 2,055,914
Grant category: Research Grants in open competition
Year: 2022
Geography: Switzerland
The overall aim of Mark Mellett’s project is to shed light on the differences and the mechanisms governing regulation of IL-36 activity in both skin inflammation and viral infection.
IL-36 cytokines (a substance secreted by cells that affect the response of nearby cells) are well-known to contribute to inflammatory skin diseases in particular generalised pustular psoriasis. Yet the mechanisms regulating the activitiy of the cytokines remain poorly understood.
Mark and his team suggest that IL-36 is an important response mechanism protecting the skin against viral infection and this response is “switched on” in error in generalised pustular psoriasis. They propose to elucidate the reasons for this to better understand how pustular psoriasis is triggered.