Petkov Stefan, Chiodi Francesca
Department of Microbiology, Tumor and Cell Biology, Biomedicum, Karolinska Institutet, Solna, Sweden.
Department of Microbiology, Tumor and Cell Biology, Biomedicum, Karolinska Institutet, Solna, Sweden.
Genomics. 2022 May;114(3):110367. doi: 10.1016/j.ygeno.2022.110367. Epub 2022 Apr 14.
Differentiation of CD4+ T naïve (T) into central memory (T) cells involves extensive molecular processes. We compared the transcriptomes of CD4+ T and T cells from HIV-1 infected patients receiving early anti-retroviral therapy (ART; EA; n = 13) and controls (n = 15). Comparison of protein coding genes between T and T revealed 533 and 82 differentially expressed genes (DEGs) in controls and EA, respectively. A high degree of transcriptional complexity was detected during transition of CD4+ T to T cells in controls involving 70 TFs, 20 master regulators of T cell differentiation (TBX21, GATA3, RARA, FOXP3, RORC); in EA only 7 TFs were modulated with expression of several master regulators remaining unchanged during differentiation. Analysis of interactions between modulated TFs and target genes revealed important regulatory interactions missing in EA group. We conclude that T cell differentiation in EA patients is impaired due to reduced modulation of genes involved in transition from CD4+ T to T cells.
CD4+初始T（Tn）细胞分化为中枢记忆T（Tcm）细胞涉及广泛的分子过程。我们比较了接受早期抗逆转录病毒治疗（ART；EA组；n = 13）的HIV-1感染患者和对照组（n = 15）的CD4+ Tn和Tcm细胞的转录组。Tn和Tcm之间蛋白质编码基因的比较显示，对照组和EA组分别有533个和82个差异表达基因（DEG）。在对照组CD4+ Tn向Tcm细胞转变过程中检测到高度的转录复杂性，涉及70个转录因子（TF）、20个T细胞分化的主要调节因子（TBX21、GATA3、RARA、FOXP3、RORC）；在EA组中，只有7个TF被调节，而几个主要调节因子的表达在分化过程中保持不变。对调节的TF与靶基因之间相互作用进行分析，发现EA组中缺少重要的调控相互作用。我们得出结论，EA患者的T细胞分化受损，原因是参与从CD4+ Tn向Tcm细胞转变的基因调节减少。
