GARP (LRRC32) is essential for the surface expression of latent TGF-β on platelets and activated FOXP3<superscript>+</superscript> regulatory T cells.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 106 (2009-08-11), Heft 32, S. 13445-13450
academicJournal
Zugriff:
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+ 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. [ABSTRACT FROM AUTHOR]
Titel: |
GARP (LRRC32) is essential for the surface expression of latent TGF-β on platelets and activated FOXP3<superscript>+</superscript> regulatory T cells.
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Autor/in / Beteiligte Person: | Tran, Dat Q. ; Andersson, John ; Wang, Rui ; Ramsey, Heather ; Unutmaz, Derya ; Shevach, Ethan M. |
Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 106 (2009-08-11), Heft 32, S. 13445-13450 |
Veröffentlichung: | 2009 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.0901944106 |
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