TGF‐β in the Immune Response

Transforming growth factor-β (TGF-β) is a highly evolutionally conserved cytokine that is critical for embryogenesis, cancer and matrix formation and immune responses. Three distinct isoforms, TGF-β1, 2 and 3, are found in mammals. TGF-β is secreted by immune and nonhematopoietic cells and acts on virtually all cell types through ubiquitously expressed receptors, which transduce the TGF-β signal through canonical Smad-dependent pathway and noncanonical Smad-independent pathways. In particular, TGF-β plays a crucial role in immune tolerance and maintains immune homeostasis by inhibiting proliferation, differentiation, activation and effector function of immune cells. On the other side of the coin, TGF-β can display proinflammatory properties, depending on the context. The more complete understanding of the various functions of TGF-β in the immune system, especially in tolerance, will enable us to design more specific and effective therapies for immune disorders. Key Concepts TGF-β is a multifunctional cytokine that mainly suppresses immune responses to maintain immune homeostasis. TGF-β signalling is transduced via not only its unique protein, Smad, but also via Smad-independent pathways. T cells are the major targets of TGF-β in immune system and its activation/proliferation, apoptosis and differentiation are regulated by TGF-β. TGF-β is a key mediator for the regulation of autoimmune diseases. Keywords: TGF-β; immune tolerance; autoimmune disease; helper T cell differentiation; regulatory T cell