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. Author manuscript; available in PMC: 2009 Jun 15.
Published in final edited form as: Semin Immunol. 2007 Nov 28;19(6):409–417. doi: 10.1016/j.smim.2007.10.011

Figure 3. The cytokine milieu influences the balance of differentiating inducible Treg and Th17 cells.

Figure 3

Inductive effects of TGF-β alone (left), with IL-2 and RA (top), and with IL-6, IL-21 and IL-23 (bottom). The left panel represents a hypothetical metastable state, induced by TGF-β, which would allow the cell to differentiate into either the Th17 or Treg lineage depending on the associated cytokines. At the metastable state, TGF-β is able to induce both RORγt and Foxp3, however, RORγt activity is inhibited by Foxp3 through an interaction of the two proteins, which ensures no IL-17 expression. Upon continued stimulation with TGF-β in the absence of proinflammatory cytokines and in the presence of IL-2 and RA, cells will differentiate into the iTreg lineage. On the other hand, if proinflammatory cytokines are present, Foxp3 expression/activity will diminish and RORγt expression will increase, tipping the “balance” towards the Th17 lineage.