IL-35, which is composed of IL-12 subunit p35 (IL-12α) and IL-27 subunit β (Ebi3), is produced predominantly by Tregs and is required for their maximal suppressive activity.[38] IL-35 treatment in vitro can suppress T cell proliferation and convert naive T cells into IL-35-producing induced Tregs (iTr35 cells) that do not express Foxp3.[39] Surprisingly, neither Ebi3 -/- nor Il12a-/- mice have overt autoimmunity or inflammatory diseases.[38] It is possible that the defect of IL-35 action in these mice is counterbalanced by the loss of inflammatory IL-12 family cytokines. This evidence concerns the gene EBI3 and Autoimmunity.