GARP (LRRC32) is essential for the surface expression of latent TGF-β on platelets and activated FOXP3 <sup>+</sup> regulatory T cells

DOI Web Site 12 Citations
  • Dat Q. Tran
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
  • John Andersson
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
  • Rui Wang
    Department of Microbiology, New York University School of Medicine, New York, NY 10016
  • Heather Ramsey
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
  • Derya Unutmaz
    Department of Microbiology, New York University School of Medicine, New York, NY 10016
  • Ethan M. Shevach
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and

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<jats:p> TGF-β family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-β is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGFβ-binding protein (LTBP) to produce a large latent form. Latent TGF-β is also found on the surface of activated FOXP3 <jats:sup>+</jats:sup> regulatory T cells (Tregs), but it is unclear how it is anchored to the cell membrane. We show that GARP or LRRC32, a leucine-rich repeat molecule of unknown function, is critical for tethering TGF-β to the cell surface. We demonstrate that platelets and activated Tregs co-express latent TGF-β and GARP on their membranes. The knockdown of GARP mRNA with siRNA prevented surface latent TGF-β expression on activated Tregs and recombinant latent TGF-β1 is able to bind directly with GARP. Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-β on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism. </jats:p>

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