Structural and functional characterization of a TGFβ molecule from amphioxus reveals an ancient origin of both immune-enhancing and -inhibitory functions.

Transforming growth factor beta (TGFβ) is a pleiotropic cytokine with important roles in mediating inflammatory response. TGFβ has been shown to be widely present in invertebrates, but little is known about its functions in immune and inflammatory responses. Moreover, structural and functional insights into TGFβ molecules in invertebrates remain completely lacking. Here we demonstrate the presence of a single TGFβ-like gene in the amphioxus Branchiostoma japonicum, Bjtgfβ, which represents the archetype of vertebrate TGFβ proteins, and displays a higher expression in the hind-gut, hepatic caecum, ovary, and gill. We also show that amphioxus TGFβ exerts both enhancing and suppressing effects on the migration of macrophages like RAW264.7, and the motif WSTD is important for TGFβ in inducing or inhibiting the migration of macrophages. Altogether, these data suggest that amphioxus TGFβ is phylogenetically and functionally similar to vertebrate TGFβ, suggesting an ancient origin of bipolar function of TGFβ proteins.