OX40 signaling directly triggers the antitumor effects of NKT cells
J. Clin. Invest. Dapeng Zhou, et al. 117:3169 doi:10.1172/JCI33976 [
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Figure 1Crosstalk between OX40L-DCs and NKT cells. It is hypothesized that OX40L-DCs first stimulate NKT cells (i) to proliferate and produce cytokines (ii). Subsequently, NKT cells activate DCs through cellular contacts (such as CD40/CD40L binding) and cytokine expression (iii), which induce the DCs to secret IL-12 and to upregulate costimulatory molecules such as CD80 and CD86. IL-12 stimulates the IL-12 receptor expressed by activated NKT cells (iv), which further potentiates NKT cell activation and forms a positive-feedback loop. Three lines of signaling transduction pathways are speculated to be activated in NKT cells: (a) TCR (Vα14 in mouse and Vα24 in human) signaling is assumed to be the first signaling pathway; (b) other costimulatory signaling networks such as CD28 might be involved and interact with both the TCR signaling network and the OX40 signaling network; and (c) OX40 signaling components may control the fate of NKT cells through molecular interactions with the TCR signaling network. OX40 interacts with TNF receptor–associated factors and may lead to the regulation of transcription factors such as NF-AT, NF-κB, and T-bet.
