Details

Autor(en) / Beteiligte

• Tran, Dat Q.
• Andersson, John
• Wang, Rui
• Ramsey, Heather
• Unutmaz, Derya
• Shevach, Ethan M.
• Littman, Dan R.

Titel

GARP (LRRC32) Is Essential for the Surface Expression of Latent TGF-β on Platelets and Activated FOXP3⁺ Regulatory T Cells

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2009-08, Vol.106 (32), p.13445-13450

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2009

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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.