Although they do not constitutively express Foxp3 (Vieira et al., 2004), and can be generated in FOXP3 mutant patients with IPEX syndrome (Passerini et al., 2011), they are able to mediate their suppressive function through multiple mechanisms, such as engagement of CTLA-4 and Programed cell death 1 (PD1) (Akdis et al., 2004; Meiler et al., 2008), metabolic disruption through CD39 and CD73 (Mandapathil et al., 2010), and cytolysis of APCs through release of granzyme B and perforin (Magnani et al., 2011). This evidence concerns the gene FOXP3 and immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.