Deciphering the neuro-immunological role of the IL-31/IL-31 receptor axis in atopic dermatitis

• Applicant: Dr. Torben Ramcke
• Subject Area: Dermatology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 524345108

Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin diseases worldwide, characterized by recurrent eczema and severe pruritus. Recently, the introduction of the monoclonal antibody Nemolizumab, which specifically antagonizes IL-31-receptor-signaling, represents a novel potent therapy concept. In addition to improve inflammatory skin lesions, Nemolizumab efficiently alleviates the excruciating itch of AD patients. It is well characterized that IL-31 mediates itch sensation by activating the IL-31 receptor on afferent cutaneous neurons. However, many aspects of the basic biology of IL-31 and its receptor remain poorly studied, especially its implications on the (neuro-) cutaneous inflammation; the key driver of AD. To shed more light on this, the first aim of this project is to characterize precisely which cell types (immune cells and non-immune cells) have the potential to secrete IL-31 and which cell populations express the IL-31 receptor under steady-state conditions and in murine AD. To facilitate this, a newly-generated IL-31-IL-31R double-reporter mouse will be established. In the second part of the project, the cell-specific role of IL-31-signaling will be investigated in detail. This approach will also rely on the newly-developed reporter mouse line, which also provides the feature to silence the IL-31-receptor signaling in desired tissues. In detail, by studying conditional knock-out mice lacking the IL-31 receptor on afferent neurons, keratinocytes, or dendritic cells, it is aimed to decipher the phenotypical and neuroimmunological consequences of cell-specific IL-31-receptor depletion in murine AD. These analyses will provide a rigorous understanding of the mechanisms exerted by the IL-31/IL-31 receptor axis in murine AD and thereby offer the translational potential to develop new and more specific therapeutic strategies for AD patients.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Daniel Kaplan, Ph.D.