Towards the structural and molecular basis of signaling assemblies mediated by the pruritogenic Interleukin-31.

The ability to sense extracellular ques and communicate with neighbouring cells is important to react to the environment and maintain equilibrium. Cytokines are small proteins that modulate the activity of the immune system by binding to their dedicated receptors at the cell surface resulting in specific cellular responses. This key physiological role comes with a downside. Native and mutant forms of cytokines and their receptors are often pivotal to the initiation and progression of inflammatory disorders, cellular malignancies and cancer. Interleukin-31 (IL-31) is a recently discovered member of the IL-6 family of cytokines and is an
important molecular player in itch and allergy-related diseases such as atopic dermatitis, inflammatory bowel disease and allergic asthma. IL-31 is intimately related to another cytokine  (OSM), the role of which is not fully understood, because they both bind the same receptor. The objective of the proposed research program in molecular structural biology is to provide timely insights into the structural and molecular basis of signaling assemblies mediated by IL-31 and the principles of receptor sharing among cytokines of the IL-6 family, thereby resolving a major bottleneck in the field. Our research initiative builds upon know-how and molecular tools generated in our group. We envisage that our work will lead to a better understanding of IL-31 and impact the development of strategies to medicate diseases to which IL-31 contributes.