Lysosomal-Associated Transmembrane Protein 4B (LAPTM4B) Decreases TGF-β1 Production in Human Regulatory T Cells
(2015) Journal of Biological Chemistry — Vol. 290, n° 33, p. 20105-20116 (2015)
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- (en) Production of active TGF-β1 is one mechanism by which human regulatory T cells (Tregs) suppress immune responses. This production is regulated by glycoprotein A repetitions predominant (GARP), a transmembrane protein present on stimulated Tregs but not on other T lymphocytes (Th and CTLs). GARP forms disulfide bonds with proTGF-β1, favors its cleavage into latent inactive TGF-β1, induces the secretion and surface presentation of GARP·latent TGF-β1 complexes, and is required for activation of the cytokine in Tregs. We explored whether additional Treg-specific protein(s) associated with GARP·TGF-β1 complexes regulate TGF-β1 production in Tregs. We searched for such proteins by yeast two-hybrid assay, using GARP as a bait to screen a human Treg cDNA library. We identified lysosomal-associated transmembrane protein 4B (LAPTM4B), which interacts with GARP in mammalian cells and is expressed at higher levels in Tregs than in Th cells. LAPTM4B decreases cleavage of proTGF-β1, secretion of soluble latent TGF-β1, and surface presentation of GARP·TGF-β1 complexes by Tregs but does not contribute to TGF-β1 activation. Therefore, LAPTM4B binds to GARP and is a negative regulator of TGF-β1 production in human Tregs. It may play a role in the control of immune responses by decreasing Treg immunosuppression.
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Huygens, C., Lienart, S., Dedobbeleer, O., Stockis, J., Gauthy, E., Coulie, P., & Lucas, S. (2015). Lysosomal-Associated Transmembrane Protein 4B (LAPTM4B) Decreases TGF-β1 Production in Human Regulatory T Cells. Journal of Biological Chemistry, 290(33), 20105-20116. https://doi.org/10.1074/jbc.M115.655340 (Original work published 2015)