胸腺基质淋巴细胞生成素
肿瘤坏死因子α
免疫学
细胞生物学
T细胞
树突状细胞
间质细胞
白细胞介素12
炎症
生物
癌症研究
细胞毒性T细胞
免疫系统
体外
生物化学
作者
Tomoki� Ito,Yui-Hsi Wang,Omar Duramad,Toshiyuki Hori,Guy Delespesse,Norihiko Watanabe,F. Xiao‐Feng Qin,Zhengbin Yao,Wei Cao,Yong‐Jun Liu
摘要
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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