Department of Immunology, University Hospital Zurich, 8091 Zurich, Switzerland; Faculty of Medicine, University of Zurich, 8032 Zurich, Switzerland; Center of Human Immunology, University of Zurich, 8006 Zurich, Switzerland.
Department of Immunology, University Hospital Zurich, 8091 Zurich, Switzerland.
Immunity. 2024 Sep 10;57(9):2232-2250.e10. doi: 10.1016/j.immuni.2024.07.016. Epub 2024 Aug 12.
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.
由于其对免疫调节 CD4 调节性 T (Treg) 细胞的刺激潜力，低剂量白细胞介素-2 (IL-2) 免疫疗法因其治疗自身免疫性疾病的潜力而受到广泛关注。在这项由研究者发起的、针对系统性红斑狼疮 (SLE) 患者的低剂量 IL-2 免疫疗法的单臂非安慰剂对照 2 期临床试验中，我们生成了低剂量 IL-2 对体内人类免疫反应的综合图谱。我们通过成像质谱细胞术、高参数流式细胞术、转录组学和靶向血清蛋白质组学对循环和皮肤免疫细胞进行了深入研究。低剂量 IL-2 刺激了各种循环免疫细胞，包括具有皮肤归巢表型的 Treg 细胞，这些细胞在 SLE 患者的皮肤中与内皮细胞密切相互作用。对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 免疫疗法有反应的独特人类 Treg 细胞亚群。
