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

T Ito, YH Wang, O Duramad, T Hori… - The Journal of …, 2005 - rupress.org
T Ito, YH Wang, O Duramad, T Hori, GJ Delespesse, N Watanabe, FXF Qin, Z Yao, W Cao
The Journal of experimental medicine, 2005rupress.org
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-α (TNF-α), 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 …
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-α (TNF-α), 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-α, 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-α, 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-α–producing inflammatory Th cell responses.
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