Release of active TGF-?1 from the latent TGF-?1/GARP complex on T regulatory cells is mediated by integrin ?8.

ABSTRACT: Activated T regulatory cells (Tregs) express latent TGF-?1 on their cell surface bound to GARP. Although integrins have been implicated in mediating the release of active TGF-?1 from the complex of latent TGF-?1 and latent TGF-?1 binding protein, their role in processing latent TGF-?1 from the latent TGF-?1/GARP complex is unclear. Mouse CD4(+)Foxp3(+) Treg, but not CD4(+)Foxp3(-) T cells, expressed integrin ?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-?1 to drive Th17 or induced Treg differentiation in vitro. In addition, Itgb8 knockout Tregs expressed higher levels of latent TGF-?1 on their cell surface consistent with defective processing. Thus, integrin ?v?8 is a marker of tTregs and functions in a cell intrinsic manner in mediating the processing of latent TGF-?1 from the latent TGF-?1/GARP complex on the surface of tTregs.

SUBMITTER: Edwards JP 

PROVIDER: S-EPMC4157079 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature