Department of Medicine, University of California at San Francisco, San Francisco, California, USA.
Nat Immunol. 2011 Oct 23;12(12):1184-93. doi: 10.1038/ni.2135.
Dendritic cells (DCs), which are known to support immune activation during infection, may also regulate immune homeostasis in resting animals. Here we show that mice lacking the ubiquitin-editing molecule A20 specifically in DCs spontaneously showed DC activation and population expansion of activated T cells. Analysis of DC-specific epistasis in compound mice lacking both A20 and the signaling adaptor MyD88 specifically in DCs showed that A20 restricted both MyD88-independent signals, which drive activation of DCs and T cells, and MyD88-dependent signals, which drive population expansion of T cells. In addition, mice lacking A20 specifically in DCs spontaneously developed lymphocyte-dependent colitis, seronegative ankylosing arthritis and enthesitis, conditions stereotypical of human inflammatory bowel disease (IBD). Our findings indicate that DCs need A20 to preserve immune quiescence and suggest that A20-dependent DC functions may underlie IBD and IBD-associated arthritides.
树突状细胞 (DCs) 在感染期间被认为支持免疫激活，也可能调节静止动物的免疫稳态。在这里，我们表明，特异性缺乏 DC 中泛素编辑分子 A20 的小鼠自发地表现出 DC 激活和活化 T 细胞的群体扩张。在缺乏 A20 和信号适配器 MyD88 的 DC 特异性复合小鼠中分析 DC 特异性上位性表明，A20 限制了驱动 DC 和 T 细胞激活的 MyD88 非依赖性信号，以及驱动 T 细胞群体扩张的 MyD88 依赖性信号。此外，特异性缺乏 DC 中 A20 的小鼠自发地发展出淋巴细胞依赖性结肠炎、血清阴性的强直性脊柱炎和附着点炎，这些都是人类炎症性肠病 (IBD) 的典型特征。我们的研究结果表明，DCs 需要 A20 来维持免疫静止，并表明 A20 依赖的 DC 功能可能是 IBD 和 IBD 相关关节炎的基础。
