Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Department of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA.
Immunity. 2014 Apr 17;40(4):569-81. doi: 10.1016/j.immuni.2014.02.012.
Foxp3(+) T regulatory (Treg) cells regulate immune responses and maintain self-tolerance. Recent work shows that Treg cells are comprised of many subpopulations with specialized regulatory functions. Here we identified Foxp3(+) T cells expressing the coinhibitory molecule TIGIT as a distinct Treg cell subset that specifically suppresses proinflammatory T helper 1 (Th1) and Th17 cell, but not Th2 cell responses. Transcriptional profiling characterized TIGIT(+) Treg cells as an activated Treg cell subset with high expression of Treg signature genes. Ligation of TIGIT on Treg cells induced expression of the effector molecule fibrinogen-like protein 2 (Fgl2), which promoted Treg-cell-mediated suppression of T effector cell proliferation. In addition, Fgl2 was necessary to prevent suppression of Th2 cytokine production in a model of allergic airway inflammation. TIGIT expression therefore identifies a Treg cell subset that demonstrates selectivity for suppression of Th1 and Th17 cell but not Th2 cell responses.
Foxp3(+) T 调节性 (Treg) 细胞调节免疫反应并维持自身耐受。最近的工作表明，Treg 细胞由具有专门调节功能的许多亚群组成。在这里，我们鉴定出表达共抑制分子 TIGIT 的 Foxp3(+) T 细胞作为一个独特的 Treg 细胞亚群，特异性抑制促炎辅助性 T 细胞 1 (Th1) 和 Th17 细胞，但不抑制 Th2 细胞反应。转录谱特征表明 TIGIT(+) Treg 细胞是一种激活的 Treg 细胞亚群，高表达 Treg 特征基因。TIGIT 在 Treg 细胞上的配体结合诱导效应分子纤维蛋白原样蛋白 2 (Fgl2) 的表达，从而促进 Treg 细胞介导的 T 效应细胞增殖抑制。此外，Fgl2 对于防止在变应性气道炎症模型中抑制 Th2 细胞因子产生是必需的。因此，TIGIT 表达鉴定了一个 Treg 细胞亚群，其显示对 Th1 和 Th17 细胞反应的选择性抑制，但不抑制 Th2 细胞反应。
