FOXP3: Required but Not Sufficient. The Role of GARP (LRRC32) as a Safeguard of the Regulatory Phenotype

FOXP3 is essential for the development and function of regulatory CD4+CD25hi T (Treg) cells. However, recent evidence suggests that FOXP3 alone is not sufficient to completely explain the regulatory phenotype of these key players in autoimmunity and inflammation: after being activated, conventional human CD4+ T cells transiently up-regulate FOXP3 without acquiring a regulatory function. Researchers have recently found that glycoprotein A repetitions predominantly (GARP, or LRRC32) is a Treg-specific receptor that binds latent TGF-β and dominantly controls FOXP3 and the regulatory phenotype via a positive feedback loop. This finding provides a missing link in our molecular understanding of FOXP3 in Treg cells. This viewpoint focuses on GARP as safeguard of FOXP3 and the regulatory phenotype.