The Journal of Immunology · 2008 · 352 citations · 25 references
Life SciencesCell BiologyImmunologyCellular ImmunologyImmunoregulationTranscriptional RegulationCytokine BiologyHelper T Cell SubsetsImmune RegulationRegulatory T CellsT Cell BiologyT Cell DifferentiationEffector T Cell DifferentiationInterleukin-2 Signaling In T Cell DifferentiationNaive T CellsNatural Regulatory T CellsT Cell Differentiation SignalingT Helper 17 DifferentiationTh17 Cell DifferentiationTransforming Growth Factor Beta Signaling In T Cell Differentiation
TGF-beta has pleiotropic effects on T cell differentiation that are determined by other cytokines in the local environment. Whereas IL-2 and TGF-beta induce naive T cells to become forkhead/winged helix transcription factor (Foxp3) positive regulatory cells (iTregs), the combination of IL-6 and TGF-beta induces IL-17-producing cells (Th17). Moreover, IL-6 can use TGF-beta produced by thymus-derived natural regulatory T cells (nTregs) to convert them to Th17 cells. In this study, we report a major difference between iTregs and nTregs. Treatment of iTregs with IL-6 did not affect Foxp3 expression, and their suppressive activity in vitro and in vivo was intact. To explain this difference between nTregs and iTregs, we found that IL-2 and TGF-beta down-regulate IL-6 receptor expression and IL-6 signaling. The resistance of iTregs to Th17 conversion suggests that they can function more effectively than nTregs in an inflammatory milieu and emphasizes the central role of IL-2 in combination with TGF-beta to maintain immunologic homeostasis.
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A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Heon Park, Zhaoxia Li, Xuexian O. Yang et al. · Nature Immunology · 2005 · 4.2K citations · Full text