Abstract：
Due to its stimulatory potential for immunomodulatory CD4+ regulatory T (Treg) cells, low-dose interleukin-2 (IL-2) immunotherapy has gained considerable attention for the treatment of autoimmune diseases. In this investigator-initiated single-arm non-placebo-controlled phase-2 clinical trial of low-dose IL-2 immunotherapy in systemic lupus erythematosus (SLE) patients, we generated a comprehensive atlas of in vivo human immune responses to low-dose IL-2. We performed an in-depth study of circulating and cutaneous immune cells by imaging mass cytometry, high-parameter flow cytometry, transcriptomics, and targeted serum proteomics. Low-dose IL-2 stimulated various circulating immune cells, including Treg cells with a skin-homing phenotype that appeared in the skin of SLE patients in close interaction with endothelial cells. Analysis of surface proteins and transcriptomes revealed different IL-2-driven Treg cell activation programs, including gut-homing CD38+, skin-homing HLA-DR+, and highly proliferative inflammation-homing CD38+ HLA-DR+ Treg cells. Collectively, these data define the distinct human Treg cell subsets that are responsive to IL-2 immunotherapy.
摘要：
由于其对免疫调节性CD4+调节性T（Treg）细胞的刺激潜力，低剂量白细胞介素-2（IL-2）免疫疗法在自身免疫性疾病的治疗中得到了广泛的关注。在这项研究人员发起的单臂非安慰剂对照2期临床试验中，系统性红斑狼疮（SLE）患者低剂量IL-2免疫疗法，我们生成了一个全面的人体对低剂量IL-2的体内免疫反应图集。我们通过成像质量细胞仪对循环和皮肤免疫细胞进行了深入研究，高参数流式细胞术，转录组学，和靶向血清蛋白质组学。低剂量IL-2刺激各种循环免疫细胞，包括在SLE患者皮肤中出现的具有皮肤归巢表型的Treg细胞与内皮细胞紧密相互作用。表面蛋白和转录组的分析揭示了不同的IL-2驱动的Treg细胞激活程序，包括肠道归巢CD38+，皮肤归巢HLA-DR+，和高度增殖的炎症归巢CD38+HLA-DR+Treg细胞。总的来说，这些数据定义了对IL-2免疫疗法有反应的不同的人Treg细胞亚群.
