Siewert Christiane, Menning Astrid, Dudda Jan, Siegmund Kerstin, Lauer Uta, Floess Stefan, Campbell Daniel J, Hamann Alf, Huehn Jochen
Experimentelle Rheumatologie, Charité Universitaetsmedizin Berlin, Berlin, Germany.
Eur J Immunol. 2007 Apr;37(4):978-89. doi: 10.1002/eji.200636575.
Compelling evidence suggests that Foxp3(+)CD25(+)CD4(+) Treg play a fundamental role in immunoregulation. We have previously demonstrated that Treg have to enter peripheral tissues to suppress ongoing inflammation. However, relatively little is known about how Treg acquire the expression of homing receptors required for tissue- or inflammation-specific migration. Migratory properties of conventional naïve T cells are shaped by the tissue microenvironment and organ-specific dendritic cells during priming. Here, we show that this basic concept also holds true for CD25(+)CD4(+) Treg: Priming of Treg within peripheral LN led to the expression of selectin ligands, which facilitate migration into inflamed skin, whereas activation within mesenteric LN led to induction of the integrin alpha(4)beta(7), which is required for migration into mucosal tissues. Furthermore, we could establish in vitro culture systems containing either dendritic cells from mesenteric and peripheral LN, or retinoic acid and IL-12 as polarizing compounds to induce mucosa- and skin-seeking Treg, respectively. Together, our results demonstrate that Treg, similarly to conventional T cells, can be configured with organ-selective homing properties allowing efficient targeting into distinct tissues.
有力证据表明，Foxp3(+)CD25(+)CD4(+)调节性T细胞在免疫调节中发挥着重要作用。我们之前已经证明，调节性T细胞必须进入外周组织才能抑制正在进行的炎症反应。然而，对于调节性T细胞如何获得组织或炎症特异性迁移所需的归巢受体的表达，我们了解得还相对较少。传统幼稚T细胞的迁移特性在启动过程中由组织微环境和器官特异性树突状细胞塑造。在这里，我们表明这个基本概念同样适用于CD25(+)CD4(+)调节性T细胞：外周淋巴结内调节性T细胞的启动导致选择素配体的表达，这有助于迁移到炎症皮肤中，而肠系膜淋巴结内的激活导致整合素α(4)β(7)的诱导，这是迁移到粘膜组织所必需的。此外，我们可以建立体外培养系统，分别包含来自肠系膜和外周淋巴结的树突状细胞，或视黄酸和白细胞介素-12作为极化化合物，以诱导归巢到粘膜和皮肤的调节性T细胞。总之，我们的结果表明，与传统T细胞类似，调节性T细胞可以被配置成具有器官选择性归巢特性，从而能够有效地靶向不同的组织。
