Cutting edge: Foxp3+ CD4+ CD25+ regulatory T cells induced by IL-2 and TGF-β are resistant to Th17 conversion by IL-6

Song Guo Zheng, Juhua Wang, David A. Horwitz

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263 Scopus citations


TGF-β has pleiotropic effects on T cell differentiation that are determined by other cytokines in the local environment. Whereas IL-2 and TGF-β induce naive T cells to become forkhead/winged helix transcription factor (Foxp3) positive regulatory cells (iTregs), the combination of IL-6 and TGF-β induces IL-17-producing cells (Tbl7). Moreover, IL-6 can use TGF-β 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 n Tregs. 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-β 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-β to maintain immunologic homeostasis.

Original languageEnglish (US)
Pages (from-to)7112-7116
Number of pages5
JournalJournal of Immunology
Issue number11
StatePublished - 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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