Dendritic cells (DCs) are the major specialized antigen-presenting cells, thereby connecting innate and adaptive immunity. Because of their role in establishing adaptive immunity, they constitute promising targets for immunotherapy. Monocytes can differentiate into DCs in vitro in the presence of colony-stimulating factor 2 (CSF2) and interleukin 4 (IL4), activating four signalling pathways (MAPK, JAK/STAT, NFKB and PI3K). However, the downstream transcriptional programme responsible for DC differentiation from monocytes (moDCs) remains unknown. By analysing the scientific literature on moDC differentiation, we established a preliminary logical model that helped us identify missing information regarding the activation of genes responsible for this differentiation, including missing targets for key transcription factors (TFs). Using ChIP-seq and RNA-seq data from the Blueprint consortium, we defined active and inactive promoters, together with differentially expressed genes in monocytes, moDCs and macrophages, which correspond to an alternative cell fate. We then used this functional genomic information to predict novel targets for previously identified TFs. By integrating this information, we refined our model and recapitulated the main established facts regarding moDC differentiation. Prospectively, the resulting model should be useful to develop novel immunotherapies targeting moDCs.

树突状细胞 (DC) 是主要的特化抗原呈递细胞，从而连接先天免疫和适应性免疫。由于它们在建立适应性免疫中的作用，它们构成了免疫治疗的有希望的靶点。单核细胞可以在体外分化成 DC在集落刺激因子 2 (CSF2) 和白细胞介素 4 (IL4) 存在的情况下，激活四种信号通路（MAPK、JAK/STAT、NFKB 和 PI3K）。然而，负责 DC 从单核细胞 (moDC) 分化的下游转录程序仍然未知。通过分析有关 moDC 分化的科学文献，我们建立了一个初步的逻辑模型，帮助我们识别有关导致这种分化的基因激活的缺失信息，包括关键转录因子 (TF) 的缺失靶标。使用 Blueprint 联盟的 ChIP-seq 和 RNA-seq 数据，我们定义了活性和非活性启动子，以及单核细胞、moDCs 和巨噬细胞中的差异表达基因，它们对应于另一种细胞命运。然后，我们使用此功能基因组信息来预测先前确定的 TF 的新靶标。通过整合这些信息，我们改进了我们的模型并概括了关于 moDC 分化的主要既定事实。展望未来，由此产生的模型应该有助于开发针对 moDCs 的新型免疫疗法。