期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：32
页码：13445-13450
DOI：10.1073/pnas.0901944106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：TGF-{beta} family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-{beta} is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGF{beta}-binding protein (LTBP) to produce a large latent form. Latent TGF-{beta} is also found on the surface of activated FOXP3+ 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-{beta} to the cell surface. We demonstrate that platelets and activated Tregs co-express latent TGF-{beta} and GARP on their membranes. The knockdown of GARP mRNA with siRNA prevented surface latent TGF-{beta} expression on activated Tregs and recombinant latent TGF-{beta}1 is able to bind directly with GARP. Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-{beta} on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism.
