A Mechanism for Regulating Pulmonary Inflammation and Fibrosis: The Integrin αvβ6 Binds and Activates Latent TGF β1

Transforming growth factor β (TGF β) family members are secreted in inactive complexes with a latency-associated peptide (LAP), a protein derived from the N-terminal region of the TGF β gene product. Extracellular activation of these complexes is a critical but incompletely understood step in regulation of TGF β function in vivo. We show that TGF β 1 LAP is a ligand for the integrin α vβ 6 and that α vβ 6-expressing cells induce spatially restricted activation of TGF β 1. This finding explains why mice lacking this integrin develop exaggerated inflammation and, as we show, are protected from pulmonary fibrosis. These data identify a novel mechanism for locally regulating TGF β 1 function in vivo by regulating expression of the α vβ 6 integrin.