Title:Dissecting the Mechanisms of Intestinal Immune Homeostasis by
Analyzing T-Cell Immune Response in Crohn's Disease and Colorectal
Cancer
Volume: 24
Issue: 5
Author(s): Tianming Jiang, Jie Zheng, Nana Li, Xiaodong Li, Jixing He, Junde Zhou, Boshi Sun*Qiang Chi*
Affiliation:
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang,
China
- Division of Surgical Oncology, Department of Surgery, Yale University School of Medicine, New
Haven, CT06510, USA
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang,
China
Keywords:
Crohn's disease, colorectal cancer, immune microenvironment, scRNA-seq, T-cell responding, homeostasis.
Abstract:
Introduction: Crohn's disease (CD) and colorectal cancer (CRC) represent a group of
intestinal disorders characterized by intricate pathogenic mechanisms linked to the disruption of intestinal
immune homeostasis. Therefore, comprehending the immune response mechanisms in
both categories of intestinal disorders is of paramount significance in the prevention and treatment
of these debilitating intestinal ailments.
Method: IIn this study, we conducted single-cell analysis on paired samples obtained from primary
colorectal tumors and individuals with Crohn's disease, which was aimed at deciphering the
factors influencing the composition of the intestinal immune microenvironment. By aligning T
cells across different tissues, we identified various T cell subtypes, such as γδ T cell, NK T cell,
and regulatory T (Treg) cell, which maintained immune system homeostasis and were confirmed
in enrichment analyses. Subsequently, we generated pseudo-time trajectories for subclusters of T
cells in both syndromes to delineate their differentiation patterns and identify key driver genes
Result: Furthermore, cellular communication and transcription factor regulatory networks are all
essential components of the intricate web of mechanisms that regulate intestinal immune homeostasis.
The identified complex cellular interaction suggested potential T-lineage immunotherapeutic
targets against epithelial cells with high copy number variation (CNV) levels in CD and CRC.
Conclusion: Finally, the analysis of regulon networks revealed several promising candidates for
cell-specific transcription factors (TFs). This study focused on the immune molecular mechanism
under intestinal diseases. It contributed to the novel insight of depicting a detailed immune landscape
and revealing T-cell responding mechanisms in CD and CRC.
