Interleukin-36 and Its Receptor

I am exploring how the pro-inflammatory cytokine interleukin-36 can become activated and the structural features of the receptor and the cytokine that allow activation to be recognised in vivo.

Interleukin (IL)-36 is a group of three homologous IL-1-like cytokines that share a unique receptor (IL1RL2), which is expressed on many epithelial cells, particularly skin, gut and airways. IL1RL2 seems to share its mechanism and its co-receptor with IL-1 receptor but there is no overlap between their ligand specificity. Dysregulated responses to IL-36 are associated with chronic or episodic inflammation of epithelia.

IL-36 proteins are produced as inactive precursors in the cytoplasm. Specific processed forms are potent pro-inflammatory stimuli on cells that bear the IL-36 receptor. There is currently only a rudimentary understanding of the unique function for IL-36 within the immune system. There is still much to be discovered concerning the pathways that naturally stimulate IL-36 protein expression, lead to its release from the cell and its activation by proteolytic processing.

The PhD project will be directed towards our continuing investigation of the activation of IL-36 expression and the structural details of the interaction of IL-36 and its receptor that allow recognition of precisely processed products.