Interleukin-2 immunotherapy reveals human regulatory T cell subsets with distinct functional and tissue-homing characteristics

IF 25.5 1区 医学 Q1 IMMUNOLOGY Immunity Pub Date : 2024-08-12 DOI:10.1016/j.immuni.2024.07.016
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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.

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白细胞介素-2 免疫疗法揭示了具有不同功能和组织归属特征的人类调节性 T 细胞亚群
由于低剂量白介素-2(IL-2)免疫疗法具有刺激免疫调节CD4+调节性T(Treg)细胞的潜力,因此在治疗自身免疫性疾病方面受到了广泛关注。在这项由研究者发起的系统性红斑狼疮(SLE)患者低剂量IL-2免疫疗法单臂非安慰剂对照2期临床试验中,我们绘制了一幅低剂量IL-2体内人体免疫反应综合图谱。我们通过成像质谱、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,这些细胞出现在系统性红斑狼疮患者的皮肤中,与内皮细胞密切相互作用。对表面蛋白和转录组的分析显示了不同的IL-2驱动的Treg细胞活化程序,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。这些数据共同定义了对IL-2免疫疗法有反应的不同人类Treg细胞亚群。
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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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