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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

TSLP- activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand.

We recently showed that dendritic cells (DCs) activated by thymic stromal lymphopoietin (TSLP) prime naive CD4(+) T cells to differentiate into T helper type 2 (Th2) cells that produced high amounts of tumor necrosis factor-alpha (TNF-alpha), but no interleukin (IL)-10. Here we report that TSLP induced human DCs to express OX40 ligand (OX40L) but not IL-12. TSLP- induced OX40L on DCs was required for triggering naive CD4(+) T cells to produce IL-4, -5, and -13. We further revealed the following three novel functional properties of OX40L: (a) OX40L selectively promoted TNF-alpha, but inhibited IL-10 production in developing Th2 cells; (b) OX40L lost the ability to polarize Th2 cells in the presence of IL-12; and (c) OX40L exacerbated IL-12- induced Th1 cell inflammation by promoting TNF-alpha, while inhibiting IL-10. We conclude that OX40L on TSLP-activated DCs triggers Th2 cell polarization in the absence of IL-12, and propose that OX40L can switch IL-10- producing regulatory Th cell responses into TNF-alpha-producing inflammatory Th cell responses.[1]


  1. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. Ito, T., Wang, Y.H., Duramad, O., Hori, T., Delespesse, G.J., Watanabe, N., Qin, F.X., Yao, Z., Cao, W., Liu, Y.J. J. Exp. Med. (2005) [Pubmed]
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