Transforming growth factor-β: innately bipolar

Widely heralded for depressing ongoing immune responses, renewed interest in the proficiency by which transforming growth factor β (TGF-β) not only engages but also might drive an over-reactive innate response highlights its bipolar nature. Although coordination of the development and function of Treg, in addition to direct inhibition of cellular activation, are prominent pathways by which TGF-β controls adaptive immunity, paradoxically TGF-β appears instrumental in initiation of host responses to invasion through recruitment and activation of immune cells and persuasion of Th17 lineage commitment. Nevertheless, true to its manic-depressive behavior, new evidence links TGF-β with depression of innate cells, including NK cells, and by way of a potential bridge between mast cells and Treg. Disruption of the tenuous balance between these opposing actions of TGF-β underlies immunopathogenicity.