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GARP is regulated by miRNAs and controls latent TGF-β1 production by human regulatory T cells.

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Gauthy, Emilie [UCL] Cuende Villasur, Julia [UCL] Stockis, Julie [UCL] Huygens, Caroline [UCL] Lethe, Bernard [UCL] Collet, Jean-François [UCL] Bommer, Guido [UCL] Coulie, Pierre G. [UCL] Lucas, Sophie [UCL]

GARP is a transmembrane protein present on stimulated human regulatory T lymphocytes (Tregs), but not on other T lymphocytes (Th cells). It presents the latent form of TGF-β1 on the Treg surface. We report here that GARP favors the cleavage of the pro-TGF-β1 precursor and increases the amount of secreted latent TGF-β1. Stimulated Tregs, which naturally express GARP, and Th cells transfected with GARP secrete a previously unknown form of latent TGF-β1 that is disulfide-linked to GARP. These GARP/TGF-β1 complexes are possibly shed from the T cell surface. Secretion of GARP/TGF-β1 complexes was not observed with transfected 293 cells and may thus be restricted to the T cell lineage. We conclude that in stimulated human Tregs, GARP not only displays latent TGF-β1 at the cell surface, but also increases its secretion by forming soluble disulfide-linked complexes. Moreover, we identified six microRNAs (miRNAs) that are expressed at lower levels in Treg than in Th clones and that target a short region of the GARP 3' UTR. In transfected Th cells, the presence of this region decreased GARP levels, cleavage of pro-TGF-β1, and secretion of latent TGF-β1.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2013
Language Anglais
Journal information "PLoS One" - Vol. 8, no.9, p. e76186 (Sep 30, 2013)
Peer reviewed yes
Publisher Public Library of Science ((United States) [S.l.])
e-issn 1932-6203
Publication status Publié
Affiliation UCL - SSS/DDUV - Institut de Duve
Links
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Bibliographic reference Gauthy, Emilie ; Cuende Villasur, Julia ; Stockis, Julie ; Huygens, Caroline ; Lethe, Bernard ; et. al. GARP is regulated by miRNAs and controls latent TGF-β1 production by human regulatory T cells.. In: PLoS One, Vol. 8, no.9, p. e76186 (Sep 30, 2013)
Permanent URL http://hdl.handle.net/2078.1/136450