Cutting Edge: Foxp3+CD4+CD25+ Regulatory T Cells Induced by IL-2 and TGF-β Are Resistant to Th17 Conversion by IL-6
Abstract
CUTTING EDGE IMMUNOLOGY THE OF JOURNAL Cutting Edge: Foxp3CD4CD25 Regulatory T Cells Induced by IL-2 and TGF- Are Resistant to Th17 Conversion by IL-61 Song Guo Zheng,2 Juhua Wang, and David A. Horwitz2 TGF- has pleiotropic effects on T cell differentiation that are determined by other cytokines in the local envi- ronment. Whereas IL-2 and TGF- induce naive T cells to become forkhead/winged helix transcription factor (Foxp3) positive regulatory cells (iTregs), the combination of IL-6 and TGF- induces IL-17-producing cells (Th17). Moreover, IL-6 can use TGF- produced by thy- mus-derived natural regulatory T cells (nTregs) to convert them to Th17 cells. In this study, we report a major dif- ference between iTregs and nTregs. Treatment of iTregs with IL-6 did not affect Foxp3 expression, and their sup- pressive activity in vitro and in vivo was intact. To ex- plain this difference between nTregs and iTregs, we found that IL-2 and TGF- down-regulate IL-6 receptor ex- pression and IL-6 signaling. The resistance of iTregs to Th17 conversion suggests that they can function more ef- fectively than nTregs in an inflammatory milieu and em- phasizes the central role of IL-2 in combination with TGF- to maintain immunologic homeostasis. The Journal of Immunology, 2008, 180: 7112–7116. A ntigen-activated naive T cells can become either effec- tor cells that protect the host from harmful microbial pathogens or regulatory/suppressor cells that main- tain immunologic homeostasis and prevent autoimmunity. It has become evident that cytokines such as TGF- can promote both effector and regulatory cell differentiation pathways de- pending upon other cytokines present in the local environment. T cells activated with IL-2 and TGF- become forkhead/ winged helix transcription factor (Foxp3)3 positive regulatory T cells (1, 2), whereas activation with IL-6 and TGF- results in Th17 cells (3–6). The control of these opposite differentiation pathways is not well understood and is a
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Cited By (11)
- Cytokine Overproduction, T-Cell Activation, and Defective T-Regulatory Functions Promote Nephritis in Systemic Lupus ErythematosusJournal of Biomedicine and Biotechnology · 2010
- Natural and TGF-β–induced Foxp3+CD4+ CD25+ regulatory T cells are not mirror images of each otherTrends in Immunology · 2008
- Translational mini-review series on Th17 cells: induction of interleukin-17 production by regulatory T cellsClinical & Experimental Immunology · 2010
- Dioxin and immune regulationAnnals of the New York Academy of Sciences · 2010
- Therapeutic potential of TGF-β-induced CD4+Foxp3+regulatory T cells in autoimmune diseasesAutoimmunity · 2011
- Myelin-Reactive, TGF-β–Induced Regulatory T Cells Can Be Programmed To Develop Th1-Like Effector Function but Remain Less Proinflammatory Than Myelin-Reactive Th1 Effectors and Can Suppress Pathogenic T Cell Clonal Expansion In VivoThe Journal of Immunology · 2010
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