The integrin αvβ6 binds and activates latent TGFβ1: A mechanism for regulating pulmonary inflammation and fibrosis

Abstract

Transforming growth factor β (TGFβ) family members are secreted in inactive complexes with a latency-associated peptide (LAP), a protein derived from the N-terminal region of the TGFβ gene product. Extracellular activation of these complexes is a critical but incompletely understood step in regulation of TGFβ function in vivo. We show that TGFβ1 LAP is a ligand for the integrin αvβ6 and that αvβ6-expressing cells induce spatially restricted activation of TGFβ1. 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 TGFβ1 function in vivo by regulating expression of the αvβ6 integrin.