Interleukin 35 (IL-35) is an IL-12 family cytokine produced by regulatory, but not effector, T-cells and plays a role in immune suppression. It is a dimeric protein composed of IL-12α and IL-27β chains, which are encoded by two separate genes called IL12A and EBI3, respectively. Secreted by regulatory T-cells (Tregs), IL-35 suppresses inflammatory responses of immune cells. IL-35 is not constitutively expressed in tissues, but the gene encoding IL-35 is transcribed by vascular endothelial cells, smooth muscle cells and monocytes after activation with proinflammatory stimuli.
Studies in mice show the absence of either IL-35 chain from regulatory Tregs reduces the cells' ability to suppress inflammation; this has been observed during cell culture experiments and using an experimental model for inflammatory bowel disease. To produce its suppressive effects (eg on collagen-induced arthritis), IL-35 has selective activities on different T-cell subsets; it induces proliferation of Treg cell populations but reduces activity of Th17 cell populations.