Journal of Autoimmunity ( IF 7.9 ) Pub Date : 2020-11-12 , DOI: 10.1016/j.jaut.2020.102563 Grzegorz Chodaczek 1 , Philippe P Pagni 2 , Gustaf Christoffersson 3 , Sowbarnika S Ratliff 2 , Monika Toporkiewicz 4 , Agnieszka S Wegrzyn 4 , Matthias von Herrath 2
Regulatory T cells (Tregs) have suppressive functions and play an important role in controlling inflammation and autoimmunity. The migratory capacity of Tregs determines their location and their location determines whether they inhibit the priming of naïve lymphocytes in lymphoid tissues or the effector phase of immune responses at inflamed sites. Tregs generated or expanded in vitro are currently being tested in clinics for the treatment of autoimmune disorders, however, little is known about the factors controlling their migration towards therapeutically relevant locations. In this study, we have modulated Treg dynamics using Toll-like receptor (TLR) agonists. Dynamic imaging with confocal and two-photon microscopy revealed that Tregs generated in vitro and stimulated with P3C (a TLR2 agonist) but not with R848 (a TLR7 agonist) or LPS (a TLR4 agonist) showed enhanced cell migration within splenic white pulp or draining lymph node when transferred into mice intravenously or into the footpad, respectively. In summary, our data demonstrate that Tregs are more motile in response to direct TLR stimulation in particular towards TLR2 signals. This may have implications for efficient clinical Treg induction protocols.
中文翻译:
Toll样受体刺激对调节性T细胞运动的影响
调节性T细胞(Treg)具有抑制功能,在控制炎症和自身免疫方面发挥着重要作用。 Tregs 的迁移能力决定了它们的位置,而它们的位置决定了它们是否抑制淋巴组织中幼稚淋巴细胞的启动或炎症部位免疫反应的效应阶段。目前正在临床中测试体外产生或扩增的Tregs用于治疗自身免疫性疾病,然而,人们对控制其向治疗相关位置迁移的因素知之甚少。在这项研究中,我们使用 Toll 样受体 (TLR) 激动剂调节 Treg 动力学。共焦和双光子显微镜的动态成像显示,Tregs在体外生成并用 P3C(一种 TLR2 激动剂)刺激,但不使用 R848(一种 TLR7 激动剂)或 LPS(一种 TLR4 激动剂)刺激,显示出脾白髓或引流内的细胞迁移增强分别通过静脉注射或足垫转移至小鼠体内时的淋巴结。总之,我们的数据表明,Treg 对直接 TLR 刺激(尤其是 TLR2 信号)的反应更具活力。这可能对有效的临床 Treg 诱导方案产生影响。