单细胞RNA测序揭露人FOXP3+调节性T细胞稳定性的关键调控分子（英文）

发布时间：2021-06-18 07:50

　　T淋巴细胞的异质性和可塑性对于决定免疫应答至关重要. FOXP3的稳定表达通常是调节性T（Treg）细胞的分子特征,现已有研究报道在炎症条件下Treg表现出了异质性.然而,炎症与Treg细胞抑制活性之间的相互作用仍然难以捉摸.本文利用单细胞RNA测序研究了Treg细胞对促炎性细胞因子IL-6的响应.研究者观察到在IL-6刺激后Treg细胞分为两个亚群. TIGIT阴性的Treg细胞丢失了FOXP3基因的表达,获得了类似效应性T细胞的表型,而TIGIT阳性的Treg细胞则保留了较强的免疫抑制功能.本文还通过单细胞转录组分析揭示了IL-6刺激下Treg细胞的状态变化,以及CYP1A1作为Treg细胞抑制功能和稳定性的关键调控基因. CYP1A1缺陷型Treg细胞在IL-6刺激后出现类似Th17细胞的表型.本研究发现暗示CYP1A1作为Treg细胞的一个崭新的调节分子,具有潜在的生物治疗应用潜力. 

【文章来源】：Science Bulletin. 2020,65(13)EISCICSCD

【文章页数】：11 页

【文章目录】：
1. Introduction
2. Materials and methods
    2.1. Ethical approval
    2.2. Preparation of Treg and conventional T cells from cord blood
    2.3. Lentivirus preparation and transduction
    2.4. Single-cell separation,library construction and RNA-seq
    2.5. Preprocessing single cell RNA-seq data
    2.6. Sample filtering
    2.7. Gene filtering and batch correction
    2.8. Weighted gene co-expression network analysis(WGCNA)
    2.9. Pseudotime analysis
    2.1 0. Gene set enrichment analysis(GSEA)
    2.1 1. Antibodies
    2.1 2. Flow cytometry
    2.1 3. RNA preparation and immunoblotting
    2.1 4. In vitro suppression assay and Treg cell proliferation assay
    2.1 5. Statistical analysis
    2.16.Data resources
3. Results
    3.1. FOXP3 expression is heterogeneous after IL-6 treatment
    3.2. Single-cell RNA sequencing reveals Treg cell heterogeneity
    3.3. TIGIT+Treg cells are more stable under IL-6 stimulation
    3.4. Unstable Treg cells have increased cell proliferation and pro-inflammatory cytokine expression
    3.5. Stable Treg cells have elevated expression of receptors and signaling toward inflammation signals
    3.6. Co-expression network analysis reveals CYP1A1 as a critical regulator of Treg cell function
    3.7. CYP1A1 is an important regulator of human Treg cell function
4. Discussion and conclusion
Conflict of interest
Author contributions
Appendix A.Supplementary materials



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