Cryo-EM structure of the IL-10 receptor complex provides a blueprint for ligand engineering.

Interleukin-10 (IL-10) is an immunomodulatory cytokine that plays important roles in terminating inflammatory responses and preventing tissue damage resulting from autoimmunity. Although these anti-inflammatory actions have led to considerable clinical interest, efforts to exploit IL-10 therapeutically have been hindered by the highly pleiotropic nature of IL-10 and its ability to elicit proinflammatory effects in vivo. In this structural snapshot, we review the recent cryo-EM structure of the IL-10 receptor signaling complex, highlighting its unique structural features, insights into the mechanism of receptor sharing by the IL-10 cytokine family, and the implications for manipulating IL-10 signaling therapeutically.