Article

Membrane protein GARP is a receptor for latent TGF-β on the surface of activated human Treg

de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
European Journal of Immunology (Impact Factor: 4.52). 12/2009; 39(12):3315-22. DOI: 10.1002/eji.200939684
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ABSTRACT Human Treg and Th clones secrete the latent form of TGF-beta, in which the mature TGF-beta protein is bound to the latency-associated peptide (LAP), and is thereby prevented from binding to the TGF-beta receptor. We previously showed that upon TCR stimulation, human Treg clones but not Th clones produce active TGF-beta and bear LAP on their surface. Here, we show that latent TGF-beta, i.e. both LAP and mature TGF-beta, binds to glycoprotein A repetitions predominant (GARP), a transmembrane protein containing leucine rich repeats, which is present on the surface of stimulated Treg clones but not on Th clones. Membrane localization of latent TGF-beta mediated by binding to GARP may be necessary for the ability of Treg to activate TGF-beta upon TCR stimulation. However, it is not sufficient as lentiviral-mediated expression of GARP in human Th cells induces binding of latent TGF-beta to the cell surface, but does not result in the production of active TGF-beta upon stimulation of these Th cells.

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    • "Although repeatedly observed in disease models (Nakamura et al., 2001) a direct contribution of TGF-β in Treg suppression remained controversial because anti-TGF-β antibodies and soluble TGF-RII failed to affect the suppressive function of Treg (Andersson et al., 2008). Recently, " glycoprotein A repetitions predominant " (GARP) expressed on the surface of Treg upon activation (Wang et al., 2008, 2009; D'Alise et al., 2011) has been shown to act as a receptor for the TGF-β/LAP complex (Stockis et al., 2009). Reminiscent of infectious Treg suppression (Jonuleit et al., 2002; Stassen et al., 2004) latent TGF-β bound to GARP on the surface of activated Treg has been demonstrated to convert responder T cells into induced Treg (Andersson et al., 2008). "
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