Acne is a common inflammatory skin disease with the dysregulation of innate and adaptive immunity. However, the underlying mechanism of acne has not been completely elucidated. In this study, we identified gene signatures and the immune-related regulatory network in acne using integrated bioinformatics methods. Here, 303 Differentially expressed genes (DEGs) and 28 Hub genes were identified in acne (GSE53795 and GSE108110), which were associated with the inflammation-related signaling pathway. Subsequently, the CIBERSORT algorithm revealed the increased proinflammatory cells in acne. Moreover, we identified 3 kinases (FGR, HCK and LYN) and 2 transcription factors (TFs) (IRF8 and ZBTB16) from DEGs as the key genes, which regulated immune cell infiltration via targeting immune-related genes in acne. The upregulated 3 kinases (FGR, HCK and LYN) and IRF8, and the downregulated ZBTB16 were also confirmed in GSE6475 and in Acne mice. Based on the expression levels of these key genes, the tissues could be divided into 2 clusters using consensus cluster analysis. GSEA analysis showed that inflammation-related signaling pathways significantly enriched in cluster 2, indicating the important role of kinase and TFs on immune regulation in acne. Finally, we found that isotretinoin and trifarotene (CD5789) treatment repressed the expression of immune genes but not the expression of the kinases and TFs, indicating that kinases and TFs may be novel therapeutic target for acne. In conclusion, 3 kinases and 2 TFs were identified and validated as key regulators in the immune-related regulatory networks in acne, providing a more comprehensive understanding and novel therapeutic targets of acne.

痤疮是一种常见的炎症性皮肤病，具有先天性和适应性免疫功能异常。但是，痤疮的潜在机制尚未完全阐明。在这项研究中，我们使用整合的生物信息学方法鉴定了痤疮的基因特征和免疫相关调节网络。在这里，痤疮（GSE53795和GSE108110）中鉴定出303个差异表达基因（DEG）和28个Hub基因，它们与炎症相关的信号通路相关。随后，CIBERSORT算法揭示了痤疮中促炎细胞的增加。此外，我们从DEGs中鉴定了3种激酶（FGR，HCK和LYN）和2种转录因子（TFs）（IRF8和ZBTB16）作为关键基因，它们通过靶向痤疮中的免疫相关基因来调节免疫细胞浸润。3种激酶（FGR，HCK和LYN）和IRF8，以及下调的ZBTB16在GSE6475和痤疮小鼠中也得到证实。根据这些关键基因的表达水平，可以使用共有聚类分析将组织分为2个聚类。GSEA分析表明，炎症相关的信号通路在簇2中显着丰富，表明激酶和TF在痤疮免疫调节中的重要作用。最后，我们发现异维A酸和trifarotene（CD5789）处理抑制免疫基因的表达，但不抑制激酶和TF的表达，表明激酶和TF可能是痤疮的新型治疗靶标。总之，已鉴定出3种激酶和2种TF作为痤疮免疫相关调控网络中的关键调控因子，