Dedobbeleer Olivier, Stockis Julie, van der Woning Bas, Coulie Pierre G, Lucas Sophie
de Duve Institute, B1200 Brussels, Belgium.
Faculty of Medicine, Catholic University of Louvain, 1348 Louvain-la-Neuve, Belgium.
J Immunol. 2017 Jul 15;199(2):391-396. doi: 10.4049/jimmunol.1601882. Epub 2017 Jun 12.
Production of active TGF-β is regulated at a posttranslational level and implies release of the mature cytokine dimer from the inactive, latent TGF-β precursor. There are several cell-type specific mechanisms of TGF-β activation. We identified a new mechanism operating on the surface of human regulatory T cells and involving membrane protein GARP, which binds latent TGF-β1. The paracrine activity of regulatory T cell-derived TGF-β1 contributes to immunosuppression and can be inhibited with anti-GARP Abs. Whether other immune cell types use surface GARP to activate latent TGF-β1 was not known. We show in this study that stimulated, human B lymphocytes produce active TGF-β1 from surface GARP/latent TGF-β1 complexes with isotype switching to IgA production.
活性转化生长因子-β（TGF-β）的产生在翻译后水平受到调控，这意味着成熟的细胞因子二聚体要从无活性的潜伏性TGF-β前体中释放出来。TGF-β的激活存在多种细胞类型特异性机制。我们发现了一种在人类调节性T细胞表面起作用且涉及膜蛋白GARP的新机制，GARP可结合潜伏性TGF-β1。调节性T细胞来源的TGF-β1的旁分泌活性有助于免疫抑制，并且可以用抗GARP抗体抑制。其他免疫细胞类型是否利用表面GARP来激活潜伏性TGF-β1尚不清楚。我们在本研究中表明，受刺激的人类B淋巴细胞可从表面GARP/潜伏性TGF-β1复合物中产生活性TGF-β1，并伴随着向产生IgA的同种型转换。
