Regulatory T cells and the induction of IL-17.

T helper (Th)17 cells have been shown to play a role in the pathogenesis of inflammatory and autoimmune diseases including inflammatory bowel diseases (IBD). It is now well established that although transforming growth factor (TGF)-beta alone induces FoxP3(+) regulatory T (Treg) cells, TGF-beta and interleukin (IL)-6, acting in concert, induce differentiation of mouse naive T cells into Th17. As we previously showed that CD4(+)CD25(+)Foxp3(+) "natural" Treg cells express cell surface or secrete TGF-beta, we examined whether Treg cells serve to induce Th17 differentiation. We found that upon activation, Treg cells induce CD4(+)CD25(-) naive T cells or Treg cells themselves to differentiate into Th17 in the presence of IL-6 alone without exogenous addition of TGF-beta. We also found that TGF-â is also produced by dendritic cells that are in contact with Treg cells. Although Treg cells are effectively recruited at inflamed mucosa in patients with IBD, it is possible that Treg cells may have undesirable effects through their ability to differentiate into pathogenic Th17 in the presence of IL-6 and/or IL-23 at sites of inflammation. Further study of the relationship between Treg cells and Th17 cells in the inflamed tissue in IBD is important for possible Treg cell-mediated therapeutic applications.