T淋巴細(xì)胞的異質(zhì)性和可塑性對(duì)于決定免疫應(yīng)答至關(guān)重要. FOXP3的穩(wěn)定表達(dá)通常是調(diào)節(jié)性T（Treg）細(xì)胞的分子特征,現(xiàn)已有研究報(bào)道在炎癥條件下Treg表現(xiàn)出了異質(zhì)性.然而,炎癥與Treg細(xì)胞抑制活性之間的相互作用仍然難以捉摸.本文利用單細(xì)胞RNA測(cè)序研究了Treg細(xì)胞對(duì)促炎性細(xì)胞因子IL-6的響應(yīng).研究者觀察到在IL-6刺激后Treg細(xì)胞分為兩個(gè)亞群. TIGIT陰性的Treg細(xì)胞丟失了FOXP3基因的表達(dá),獲得了類似效應(yīng)性T細(xì)胞的表型,而TIGIT陽(yáng)性的Treg細(xì)胞則保留了較強(qiáng)的免疫抑制功能.本文還通過(guò)單細(xì)胞轉(zhuǎn)錄組分析揭示了IL-6刺激下Treg細(xì)胞的狀態(tài)變化,以及CYP1A1作為T(mén)reg細(xì)胞抑制功能和穩(wěn)定性的關(guān)鍵調(diào)控基因. CYP1A1缺陷型Treg細(xì)胞在IL-6刺激后出現(xiàn)類似Th17細(xì)胞的表型.本研究發(fā)現(xiàn)暗示CYP1A1作為T(mén)reg細(xì)胞的一個(gè)嶄新的調(diào)節(jié)分子,具有潛在的生物治療應(yīng)用潛力. 

【文章來(lái)源】：Science Bulletin. 2020,65(13)EISCICSCD

【文章頁(yè)數(shù)】：11 頁(yè)

【文章目錄】：
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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