IL-35 is a newly described cytokine comprised of the IL-12alpha chain (p35) and the Epstein-Barr virus-induced gene product 3 (EBI-3). IL-35 belongs to the IL-12 family which includes IL-12, IL-23, IL-27, and IL-35. These cytokines are heterodimeric proteins comprised of an alpha chain (p19, p28, or p35) and a beta chain (p40 or Ebi3).
Mouse IL-35-Fc fusion protein enhances the proliferation of mouse Treg cells, while inhibiting the development of Th17 cells. Human IL-35 can suppress the proliferation of umbilical cord-derived human CD4 T conventional cells, to a similar extent as activated Tregs. In addition, activation of human CD4 T conventional cells with anti-CD3 and anti-CD28 in the presence of IL-35 induces the expression of IL-35 in these cells. Interestingly, activated T conventional cells treated with IL-35 acquire a regulatory phenotype (iTreg35) that suppress via IL-35. Most recent data suggest that IL-35 secreted by ICOS+ Tregs can suppress IL-17 production and reverse established IL-17-dependent allergic airways disease in mice.