University of Dundee

New cytokine signalling model aids understanding of autoimmune diseases

17 May 2021

Collaborative research between scientists in the Division of Cell Signalling and Immunology and the University of Leeds has been published in eLife. The work highlights a new cytokine signalling model that helps to understand how cytokine responses become dysregulated and contribute to the development of autoimmune diseases – such as Systemic Lupus Erythematosus.

IL-6 and IL-27 play a central role in maintaining inflammation homeostasis, with IL-6 exerting pro-inflammatory activities and IL-27 contributing to limit the extent of the inflammatory response. Interestingly, both cytokines share most components of their signalling pathways, raising the question of how functional specificity is achieved by IL-6 and IL-27. Using a multidisciplinary approach, the Moraga lab has probed signal propagation and output integration by these two cytokines on several levels including receptor assembly, effector activation as well as transcriptomic and proteomic changes. Their study shows that IL-27 triggers a unique signal response pattern that contributes to its anti-inflammatory activities: Sustained signalling and positive feedback loops by IL-27 ultimately changed cellular responses in a way that IL-6, could not do. These results were corroborated and validated by mathematical modelling of the IL-6 and IL-27 signalling pathways from the Molina-Paris lab in Leeds.

The research is available to read now in eLife and was supported with funding from Horizon 2020 Framework Programme, Wellcome, EPSRC, EMBO, University of Leeds, DFG and National Heart, Lung and Blood Institute.

Image caption: Experimentally characterising and mathematically modelling of cytokine signalling in health and autoimmune diseases.