Pregnancy specific glycoprotein 1 (PSG1) activates TGF-β and prevents dextran sodium sulfate (DSS)-induced colitis in mice

Transforming growth factor beta (TGF-βs) are secreted from cells as latent complexes and the activity of TGF-βs is controlled predominantly through activation of these complexes. Tolerance to the fetal allograft is essential for pregnancy success; TGF-β1 and -β2 play important roles in regulating these processes. Pregnancy-specific β-glycoproteins (PSGs) are present in the maternal circulation at high concentration throughout pregnancy and have been proposed to have anti-inflammatory functions. We found that recombinant and native PSG1 activate TGF-β1 and TGF-β2 in vitro. Consistent with these findings, administration of PSG1 protected mice from DSS-induced colitis, reduced the secretion of pro-inflammatory cytokines and increased the number of T regulatory cells. The PSG1-mediated protection was greatly inhibited by the co-administration of neutralizing anti-TGF-β Ab. Our results indicate that proteins secreted by the placenta directly contribute to the generation of active TGF-β and identify PSG1 as one of the few known biological activators of TGF-β2.