Littringer Katharina, Moresi Claudia, Rakebrandt Nikolas, Zhou Xiaobei, Schorer Michelle, Dolowschiak Tamas, Kirchner Florian, Rost Felix, Keller Christian W, McHugh Donal, LeibundGut-Landmann Salomé, Robinson Mark D, Joller Nicole
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Front Immunol. 2018 Jun 13;9:1344. doi: 10.3389/fimmu.2018.01344. eCollection 2018.
CD4Foxp3 Treg cells are essential for maintaining self-tolerance and preventing excessive immune responses. In the context of Th1 immune responses, co-expression of the Th1 transcription factor T-bet with Foxp3 is essential for Treg cells to control Th1 responses. T-bet-dependent expression of CXCR3 directs Treg cells to the site of inflammation. However, the suppressive mediators enabling effective control of Th1 responses at this site are unknown. In this study, we determined the signature of CXCR3 Treg cells arising in Th1 settings and defined universal features of Treg cells in this context using multiple Th1-dominated infection models. Our analysis defined a set of Th1-specific co-inhibitory receptors and cytotoxic molecules that are specifically expressed in Treg cells during Th1 immune responses in mice and humans. Among these, we identified the novel co-inhibitory receptor CD85k as a functional predictor for Treg-mediated suppression specifically of Th1 responses, which could be explored therapeutically for selective immune suppression in autoimmunity.
CD4Foxp3调节性T细胞对于维持自身耐受性和防止过度免疫反应至关重要。在Th1免疫反应的背景下，Th1转录因子T-bet与Foxp3的共表达对于调节性T细胞控制Th1反应至关重要。CXCR3的T-bet依赖性表达将调节性T细胞导向炎症部位。然而，在该部位能够有效控制Th1反应的抑制介质尚不清楚。在本研究中，我们确定了在Th1环境中产生的CXCR3调节性T细胞的特征，并使用多种以Th1为主导的感染模型定义了该环境下调节性T细胞的普遍特征。我们的分析确定了一组Th1特异性共抑制受体和细胞毒性分子，它们在小鼠和人类的Th1免疫反应期间在调节性T细胞中特异性表达。其中，我们鉴定出新型共抑制受体CD85k是调节性T细胞介导的对Th1反应特异性抑制的功能预测指标，这可用于自身免疫性疾病中选择性免疫抑制的治疗探索。
