Fig. 3. An integrated view of TGF-β1 in T_reg biology.

TGF-β1 is uniquely poised to be a focal point in T_reg biology because T_regs highly express the TGF-β receptor, are major producers of latent TGF-β1, and have their activating machinery. (A) Signaling through receptor dimers of TGF-βRI and TGF-βRII is a requirement for both thymic T_reg development and induced T_reg differentiation. (B) T_reg-derived TGF-β1 has long been hypothesized to have a major role in T_reg function as these cells are a source of latent TGF-β1 and express both GARP and αvβ8 integrin, which work in tandem to activate TGF-β1. Accumulating evidence suggests that T_reg-produced TGF-β1 contributes to immunoregulation but is one of several mechanisms in the T_reg arsenal. Although not critical to homeostatic function, T_reg generation of bioactive TGF-β1 is likely to have tissue- and context-specific immunomodulatory activity.