Structural and Functional Analysis of Interleukin-37 Signalling

The interleukin-1 family of cytokines are typically pro-inflammatory proteins that work together to regulate host defence. Interleukin-37 is a recently identified cytokine that is different from its other family members, since it is a broad-spectrum inhibitor of inflammation. We solved its structure at high resolution and discovered that it had a unique conformation compared to other family members. Structure-guided mutational analysis enabled generation of different forms of interleukin-37. These forms exhibited increased anti-inflammatory activity in collaborative cell-based assays and mice models compared to wild-type. These results suggest interleukin-37 and its mutants could be key targets for therapeutic development.