Cutting Edge: Regulatory T Cells Induce CD4+CD25−Foxp3− T Cells or Are Self-Induced to Become Th17 Cells in the Absence of Exogenous TGF-β

TLDR

Recent studies have shown that TGF‑β together with IL‑6 induces differentiation of IL‑17‑producing Th17 cells. We examined whether CD4+CD25+Foxp3+ regulatory T cells, known to produce TGF‑β, can act as Th17 inducers. Activated CD25+ T cells produce soluble TGF‑β and, with IL‑6, convert CD4+CD25−Foxp3− T cells into Th17 cells; moreover, the regulatory T cells themselves differentiate into Th17 cells in the absence of exogenous TGF‑β, indicating they can both induce and become Th17 cells, with implications for therapy.

Abstract

Abstract Recent studies have shown that TGF-β together with IL-6 induce the differentiation of IL-17-producing T cells (Th17) T cells. We therefore examined whether CD4+CD25+Foxp3+ regulatory T cells, i.e., cells previously shown to produce TGF-β, serve as Th17 inducers. We found that upon activation purified CD25+ T cells (or sorted GFP+ T cells obtained from Foxp3-GFP knockin mice) produce high amounts of soluble TGF-β and when cultured with CD4+CD25−Foxp3− T cells in the presence of IL-6 induce the latter to differentiate into Th17 cells. Perhaps more importantly, upon activation, CD4+CD25+Foxp3+(GFP+) T cells themselves differentiate into Th17 cells in the presence of IL-6 (and in the absence of exogenous TGF-β). These results indicate that CD4+CD25+Foxp3+ regulatory T cells can function as inducers of Th17 cells and can differentiate into Th17 cells. They thus have important implications to our understanding of regulatory T cell function and their possible therapeutic use.