Molecular Characterisation of Regulation and Mechanism of Action of the Anti-inflammatory Cytokine Interleukin 37

Direct clinical relevance: medium/low. Hands-on learning opportunities: Culture of primary human blood cells and cell lines, protein detection by ELISA, RNA detection by real-time PCR, flow cytometry, immunohistochemistry. Interleukin (IL)-37 was discovered in silico in 2000, but it remained a neglected molecule, and nothing at all was known about its function until 2010, when we described the powerful anti-inflammatory properties of this cytokine. IL-37 belongs to the IL-1 family of cytokines and imparts a strong inhibition of the production of pro-inflammatory cytokines. Interestingly, this protection from inflammatory responses is not limited to one or a few triggers, but covers a wide spectrum of inflammatory assaults - a rare property, which renders IL-37 a prime candidate for clinical use. However, further research on the mechanism of action of this unusual cytokine is required before such steps can be taken. In this project, we will characterise several aspects of regulation and function of IL-37, in particular the mRNA and protein expression profile of IL-37 across a spectrum of cell types and the effect of IL-37 one of the key molecular regulator of inflammation, the inflammasome.