Details

Autor(en) / Beteiligte

• Glinka, Yelena
• Prud’homme, Gerald J.

Titel

Neuropilin‐1 is a receptor for latent and active TGFβ‐1and is involved in suppression by regulatory T cells

Ist Teil von

• The FASEB journal, 2008-03, Vol.22 (S1)

Erscheinungsjahr

2008

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Abstract only Neuropilin‐1 (Nrp1) is a receptor for the class 3 semaphorins and vascular endothelial growth factor (VEGF). It is also a marker of regulatory T cells (Tr), which often carry both Nrp1 and latency‐associated peptide‐TGFβ‐1. The signaling TGFβ‐1 receptors bind only active TGFβ‐1, and we hypothesized that Nrp1 binds the latent form. Indeed, we found that Nrp1 is a high affinity receptor for both latent and active TGFβ‐1. Free LAP and LAP‐TGFβ‐1 competed with VEGF165 for binding to Nrp1. LAP has a basic, arginine‐rich C‐terminal motif similar to VEGF and peptides, which bind to the b1 domain of Nrp1. A C‐terminal LAP peptide (QSSRHRR) bound to Nrp1 and inhibited the binding of VEGF and LAP‐TGFβ‐1. Compared to Nrp1‐ cells, sorted Nrp1+ T cells had a much greater capacity to capture LAP‐TGFβ‐1. Sorted Nrp1‐ T cells captured soluble Nrp1‐Fc, and this increased their ability to capture LAP‐TGFβ‐1. Conventional CD4+CD25‐Nrp1‐ T cells double‐coated with Nrp1‐Fc/LAP‐TGFβ‐1 acquired strong Tr activity. Moreover, LAP‐TGFβ‐1 was activated by Nrp1‐Fc, and also by a peptide of the b2 domain of Nrp1 (RKFK; similar to a thrombospondin‐1 KRFK peptide, which is involved in LAP‐TGFβ‐1 activation). Nrp1 also activated LAP‐TGFβ‐1 in cell‐free system. Thus, Nrp1 is a receptor for latent and active TGFβ‐1, and can contribute to Tr activity.