Genome Analysis Unit, Amgen Research, Amgen Inc, South San Francisco, CA, USA.
Department of Oncology and Inflammation, Amgen Research, Amgen Inc, South San Francisco, CA, USA.
Life Sci Alliance. 2020 Apr 8;3(5). doi: 10.26508/lsa.201900520. Print 2020 May.
The therapeutic expansion of Foxp3 regulatory T cells (Tregs) shows promise for treating autoimmune and inflammatory disorders. Yet, how this treatment affects the heterogeneity and function of Tregs is not clear. Using single-cell RNA-seq analysis, we characterized 31,908 Tregs from the mice treated with a half-life extended mutant form of murine IL-2 (IL-2 mutein, IL-2M) that preferentially expanded Tregs, or mouse IgG Fc as a control. Cell clustering analysis revealed that IL-2M specifically expands multiple sub-states of Tregs with distinct expression profiles. TCR profiling with single-cell analysis uncovered Treg migration across tissues and transcriptional changes between clonally related Tregs after IL-2M treatment. Finally, we identified IL-2M-expanded Tnfrsf9Il1rl1 Tregs with superior suppressive function, highlighting the potential of IL-2M to expand highly suppressive Foxp3 Tregs.
Foxp3 调节性 T 细胞（Tregs）的治疗性扩增有望用于治疗自身免疫和炎症性疾病。然而，这种治疗方法如何影响 Tregs 的异质性和功能尚不清楚。我们使用单细胞 RNA-seq 分析，对用半衰期延长的鼠 IL-2（IL-2 突变体，IL-2M）或小鼠 IgG Fc 作为对照处理的小鼠中的 31908 个 Tregs 进行了特征描述。细胞聚类分析表明，IL-2M 特异性地扩增了具有不同表达谱的多个 Tregs 亚状态。单细胞分析的 TCR 分析揭示了 Treg 在组织间的迁移以及 IL-2M 治疗后克隆相关 Treg 之间的转录变化。最后，我们鉴定了具有优越抑制功能的 IL-2M 扩增的 Tnfrsf9Il1rl1 Tregs，突出了 IL-2M 扩增高度抑制性 Foxp3 Tregs 的潜力。
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