Menning Astrid, Höpken Uta E, Siegmund Kerstin, Lipp Martin, Hamann Alf, Huehn Jochen
Experimentelle Rheumatologie, Charité Universitätsmedizin Berlin, Berlin, Germany.
Eur J Immunol. 2007 Jun;37(6):1575-83. doi: 10.1002/eji.200737201.
Foxp3+CD25+CD4+ Treg play a fundamental role in the maintenance of self tolerance and the control of inflammatory reactions. Previous data demonstrated a division of labor between naive- and effector/memory-like Treg subsets, which is largely based on their lymph node-recirculating and inflammation-seeking migration behavior, respectively. The chemokine receptor CCR7 is expressed on both types of Treg subsets, albeit at different levels. Whether it fulfills similar or distinct roles in these subsets has not been studied so far. We here show that the recirculation of naive-like Treg through LN and, to some extent, the gut is dependent on CCR7. Lack of CCR7 not only prevents recirculation, but also almost completely abolishes the ability of naive-like Treg to control the priming phase of an immune response. In contrast, CCR7 deficiency in effector/memory-like Treg promotes their accumulation in inflamed sites, compatible with a role of CCR7 for exit from the tissue. Local Treg accumulation was accompanied by an enhanced suppression of inflammation. Together, our findings provide conclusive evidence that CCR7 expression on Treg differentially controls in vivo function of the naive- and effector/memory-like subsets.
Foxp3 + CD25 + CD4 + 调节性T细胞（Treg）在维持自身耐受性和控制炎症反应中发挥着重要作用。先前的数据表明，初始型和效应/记忆样Treg亚群之间存在分工，这在很大程度上分别基于它们在淋巴结中的再循环和向炎症部位趋化迁移的行为。趋化因子受体CCR7在这两种类型的Treg亚群中均有表达，尽管表达水平不同。到目前为止，尚未研究它在这些亚群中发挥相似还是不同的作用。我们在此表明，初始样Treg通过淋巴结以及在一定程度上通过肠道的再循环依赖于CCR7。缺乏CCR7不仅会阻止再循环，而且几乎会完全消除初始样Treg控制免疫反应启动阶段的能力。相反，效应/记忆样Treg中CCR7的缺乏会促进它们在炎症部位的积累，这与CCR7在从组织中迁出方面的作用一致。局部Treg的积累伴随着炎症抑制作用的增强。总之，我们的研究结果提供了确凿的证据，表明Treg上CCR7的表达差异地控制了初始型和效应/记忆样亚群的体内功能。
