title: Garp as a therapeutic target for modulation of T regulatory cell function.
abstract: 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.
authors.affiliation: a Laboratory of Immunology , National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , MD , USA.
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Shevach
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D016023:Integrins / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016023:Integrins; C087215:LRRC32 protein, human; D008565:Membrane Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1
keywords: GARP; T regulatory cells; foxp3; integrins; latent TGF-β; suppression