Division of Dermatology, Department of Medicine, St Louis, Missouri, USA.
J Invest Dermatol. 2010 Jan;130(1):184-91. doi: 10.1038/jid.2009.242.
Contact hypersensitivity (CHS) requires activation of the innate immune system, and results in an adaptive immune response. Many cells of the innate immune system use Toll-like receptors (TLRs), which signal through the adaptor protein, MyD88, to initiate an immune response. MyD88 is also required for signaling downstream of the IL-1 and Il-18 receptors (IL-1R and IL-18R, respectively). Herein, we studied the MyD88 signaling pathway in the CHS response to DNFB. Mice deficient in MyD88 were unable to mount a CHS response to DNFB. In contrast, mice deficient in Toll/IL-1R-containing adaptor-inducing IFN-beta, TLR2, TLR4, TLR6, and TLR9 had no defect in their ability to respond to DNFB. Although both IL-1R and IL-18R-deficient mice showed a reduced CHS response to DNFB, in bone marrow chimera and adoptive transfer experiments, we found that MyD88 and the IL-18R were required in a radioresistant cell in the sensitization phase of the CHS response. In contrast, similar strategies revealed that the IL-1R was required in a radiosensitive cell in the sensitization phase of the CHS response. Taken together, these data indicate that the IL-1R and IL-18R/MyD88 pathways are required in distinctly different cells during the sensitization phase of CHS.
接触性超敏反应 (CHS) 需要激活先天免疫系统，并导致适应性免疫反应。先天免疫系统的许多细胞都使用 Toll 样受体 (TLR)，TLR 通过衔接蛋白 MyD88 发出信号，启动免疫反应。MyD88 也是 IL-1 和 Il-18 受体 (IL-1R 和 IL-18R，分别) 下游信号传导所必需的。在此，我们研究了 MyD88 信号通路在 DNFB 诱导的 CHS 反应中的作用。MyD88 缺陷小鼠无法对 DNFB 产生 CHS 反应。相比之下，缺乏 Toll/IL-1R 包含衔接诱导 IFN-beta、TLR2、TLR4、TLR6 和 TLR9 的小鼠在对 DNFB 的反应能力上没有缺陷。尽管 IL-1R 和 IL-18R 缺陷小鼠对 DNFB 的 CHS 反应均减弱，但在骨髓嵌合体和过继转移实验中，我们发现 MyD88 和 IL-18R 在 CHS 反应的致敏阶段需要一种对辐射有抗性的细胞。相比之下，类似的策略表明，IL-1R 在 CHS 反应的致敏阶段需要一种对辐射敏感的细胞。总之，这些数据表明，IL-1R 和 IL-18R/MyD88 途径在 CHS 的致敏阶段需要在不同的细胞中发挥作用。
