Release of Active TGF- beta 1 from the Latent TGF- beta 1/GARP Complex on T Regulatory Cells Is Mediated by Integrin beta 8

Activated T regulatory cells (Tregs) express latent TGF- beta 1 on their cell surface bound to GARP. Although integrins have been implicated in mediating the release of active TGF- beta 1 from the complex of latent TGF- beta 1 and latent TGF- beta 1 binding protein, their role in processing latent T...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2014-09, Vol.193 (6), p.2843-2849
Main Authors: Edwards, Justin P, Thornton, Angela M, Shevach, Ethan M
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Activated T regulatory cells (Tregs) express latent TGF- beta 1 on their cell surface bound to GARP. Although integrins have been implicated in mediating the release of active TGF- beta 1 from the complex of latent TGF- beta 1 and latent TGF- beta 1 binding protein, their role in processing latent TGF- beta 1 from the latent TGF- beta 1/GARP complex is unclear. Mouse CD4+Foxp3+ Treg, but not CD4+Foxp3- T cells, expressed integrin beta 8 (Itgb8) as detected by quantitative RT-PCR. Itgb8 expression was a marker of thymically derived (t)Treg, because it could not be detected on Foxp3+Helios- Tregs or on Foxp3+ T cells induced in vitro. Tregs from Itgb8 conditional knockouts exhibited normal suppressor function in vitro and in vivo in a model of colitis but failed to provide TGF- beta 1 to drive Th17 or induced Treg differentiation in vitro. In addition, Itgb8 knockout Tregs expressed higher levels of latent TGF- beta 1 on their cell surface consistent with defective processing. Thus, integrin alpha v beta 8 is a marker of tTregs and functions in a cell intrinsic manner in mediating the processing of latent TGF- beta 1 from the latent TGF- beta 1/GARP complex on the surface of tTregs.
ISSN:0022-1767
DOI:10.4049/jimmunol.1401102