Dissecting the mechanisms of intestinal immune homeostasis by analyzing T-cell immune response in Crohn's disease and colorectal cancer

Abstract Background: Maintenance of intestinal immune homeostasis is intricately linked to various immune cells, signaling pathways, and molecular mechanisms. Once the intestinal immune homeostasis is out of balance, it may lead to the occurrence of intestinal diseases. Here, we performed single-cell transcriptome analysis for autologous samples from primary colorectal tumors and Crohn’s disease to disentangle factors shaping the intestinal immune microenvironment. Results: By aligning T cells across different tissues, we identified various T cell subtypes that maintained immune system homeostasis and were confirmed in enrichment analyses. Next, the pseudo-time trajectory of T cell subclusters was constructed in both syndromes so as to characterize their differentiation patterns and dig out key driver genes. Additionally, cellular communication and transcription factor regulatory networks are all critical components of the intricate web of mechanisms that regulate intestinal immune homeostasis. The complex cellular interaction suggested potential T-lineage immunotherapeutic targets against epithelial cells with high copy number variation level. Finally, regulon networks identified multiple candidates for promising cell-specific transcriptional factors. Conclusion: This study focused on the immune molecular mechanism under intestinal diseases and contributed into novel insight of depicting a detailed immune landscape and revealing T-cell responding mechanisms in Crohn’s disease and colorectal cancer.