Department of Immunology and Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, 7455 Fannin, Unit 901, Houston, TX 77030, USA.
Sci Signal. 2010 Jan 19;3(105):ra4. doi: 10.1126/scisignal.2000567.
Our adaptive immune system induces distinct responses to different pathogens because of the functional plasticity of dendritic cells (DCs); however, how DCs program unique responses remains unclear. Here, we found that the cytokine thymic stromal lymphopoietin (TSLP) potently transduced a unique T helper type 2 (T(H)2)-inducing compound signal in DCs. Whereas activation of nuclear factor kappaB (predominantly p50) drove DCs to produce OX40L to induce T(H)2 differentiation, the activation of signal transducer and activator of transcription 6 (STAT6) triggered DCs to secrete chemokines necessary for the recruitment of T(H)2 cells. In addition, TSLP signaling limited the activation of STAT4 and interferon regulatory factor 8 (IRF-8), which are essential factors for the production of the T(H)1-polarizing cytokine interleukin-12 (IL-12). By contrast, Toll-like receptor ligands and CD40 ligand did not activate STAT6 in myeloid DCs, but instead increased the abundance of STAT4 and IRF-8 to induce T(H)1 responses through the production of IL-12. Therefore, we propose that the functional plasticity of DCs relies on elaborate signal codes that are generated by different stimuli.
我们的适应性免疫系统能够针对不同的病原体产生不同的反应，这是由于树突状细胞（DCs）的功能可塑性；然而，DC 如何编程独特的反应尚不清楚。在这里，我们发现细胞因子胸腺基质淋巴细胞生成素（TSLP）在 DC 中有效地转导了一种独特的辅助性 T 细胞 2（T(H)2）诱导化合物信号。虽然核因子 kappaB（主要是 p50）的激活促使 DC 产生 OX40L 来诱导 T(H)2 分化，但信号转导和转录激活因子 6（STAT6）的激活促使 DC 分泌招募 T(H)2 细胞所必需的趋化因子。此外，TSLP 信号转导限制了 STAT4 和干扰素调节因子 8（IRF-8）的激活，后者是产生 T(H)1 极化细胞因子白细胞介素-12（IL-12）所必需的因素。相比之下，Toll 样受体配体和 CD40 配体不会在髓样 DC 中激活 STAT6，而是通过产生 IL-12 增加 STAT4 和 IRF-8 的丰度，从而诱导 T(H)1 反应。因此，我们提出 DC 的功能可塑性依赖于不同刺激产生的精细信号代码。
