Garp as a therapeutic target for modulation of T regulatory cell function

Foxp3⁺ T regulatory cells (Tregs) play critical roles in immune homeostasis primarily by suppressing many aspects of the immune response. Tregs uniquely express GARP on their cell surface and GARP functions as a delivery system for latent TGF-β. As Treg-derived TGF-β may mediate the suppressive functions of Tregs, GARP may represent a target to inhibit Treg suppression in cancer or augment suppression in autoimmunity. Areas covered: This article will focus on 1) the role of Treg-derived TGF-β in the suppressive activity of Treg, 2) the cellular and molecular regulation of expression of GARP on mouse and human Tregs, 3) the role of integrins in the activation of latent-TGF-β/GARP complex, 4) an overview of our present understanding of the function of the latent-TGF-β/GARP complex. Expert opinion: Two approaches are outlined for targeting the L-TGF-β1/GARP complex for therapeutic purposes. Tregs play a major role in suppressive effector T cell responses to tumors and TGF-β1 may be a major contributor to this process. One approach is to specifically block the production of active TGF-β1 from Tregs as an adjunct to tumor immunotherapy. The second approach in autoimmunity is to selectively enhance the production of TGF-β by Tregs at sites of chronic inflammation.