Although they were originally thought to be a subset of TH1 cells, TH17 cells are now known to differentiate independently in the presence of transforming growth factor-β (TGFβ) and IL-6, with IL-23 having a poorly characterized role in the maintenance of TH17 cells. The relationship between TH1 and TH17 cells has not been fully resolved, however, and both phenotypes are found in models of autoimmunity and infectious disease. Weaver and colleagues now show that in cultures of TH17 cells that are maintained with TGFβ, a subset of cells expresses both IL-17A and IFNγ. Under conditions of continuous IL-23 stimulation in the absence of TGFβ, the frequency of cells that express IFNγ without co-expression of IL-17A increases. So, TGFβ is required for stable expression of IL-17A, whereas in the absence of TGFβ, IL-23 induces a decrease in IL-17A expression and an increase in IFNγ expression by TH17 cells.
This transition from an IL-17- to an IFNγ-producing phenotype was shown to occur to a greater extent when the cells were stimulated with IL-12 in the absence of TGFβ. Indeed, although the addition of TGFβ blunted the effect of IL-12, IFNγ expression still became dominant despite the presence of TGFβ. So, although TH17 cells express low levels of the IL-12 receptor subunit IL-12Rβ2, the presence of IL-12 can result in a marked and rapid change in their cytokine profile.
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