TGF-β: the sword, the wand, and the shield of FOXP3(+) regulatory T cells

J Mol Cell Biol. 2012 Feb;4(1):29-37. doi: 10.1093/jmcb/mjr033. Epub 2011 Dec 8.


Since its rediscovery in the mid-1990s, FOXP3(+) regulatory T cells (Tregs) have climbed the rank to become commander-in-chief of the immune system. They possess diverse power and ability to orchestrate the immune system in time of inflammation and infection as well as in time of harmony and homeostasis. To be the commander-in-chief, they must be equipped with both offensive and defensive weaponry. This review will focus on the function of transforming growth factor-β (TGF-β) as the sword, the wand, and the shield of Tregs. Functioning as a sword, this review will begin with a discussion of the evidence that supports how Tregs utilize TGF-β to paralyze cell activation and differentiation to suppress immune response. It will next provide evidence on how TGF-β from Tregs acts as a wand to convert naïve T cells into iTregs and Th17 to aid in their combat against inflammation and infection. Lastly, the review will present evidence on the role of TGF-β produced by Tregs in providing a shield to protect and maintain Tregs against apoptosis and destabilization when surrounded by inflammation and constant stimulation. This triadic function of TGF-β empowers Tregs with the responsibility and burden to maintain homeostasis, promote immune tolerance, and regulate host defense against foreign pathogens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Cell Differentiation
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Forkhead Transcription Factors / immunology*
  • Homeostasis
  • Humans
  • Inflammation / immunology
  • Lymphocyte Activation
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Signal Transduction
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / immunology
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta / metabolism
  • Transplantation Tolerance


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • LRRC32 protein, human
  • Lrrc32 protein, mouse
  • Membrane Proteins
  • Transforming Growth Factor beta