Transforming growth factor-beta: innately bipolar

Sharon M Wahl1

  • 1Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD 20892-4352, USA. smwahl@dir.nidcr.nih.gov

Widely heralded for depressing ongoing immune responses, renewed interest in the proficiency by which transforming growth factor beta (TGF-beta) 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-beta controls adaptive immunity, paradoxically TGF-beta 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-beta 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-beta underlies immunopathogenicity.

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