Crosstalk between T cell gene regulation and intestinal epithelial cells: Insights into mucosal immunity

The intestinal epithelium serves as a critical mechanical barrier against potentially pathogenic bacteria and their antigens while maintaining immune homeostasis and facilitating nutrient and water absorption. In the gut, T cells undergo a multitude of highly specialized differentiation processes which are influenced by the unique microenvironment. Several studies reveal that intestinal epithelial cells (IECs) not only provide signals that shape T cell responses but also express a variety of factors that modulate T cell activity, such as cytokines, chemokines, and antigen-presenting molecules. The crosstalk between T cells and intestinal epithelium is necessary to grant a delicate immune balance to prevent excessive inflammation while assuring tolerance towards commensal microbial communities. Disruption of this line of communication can be deleterious since it could lead to immune-inflammatory disorders such as inflammatory bowel disease (IBD) and other disorders such as colorectal cancer. In recent years, advanced genomic and transcriptomic technologies have partially untangled the regulatory networks underlying this interaction. Understanding how the mechanisms governing the regulation of the interaction between T cells and IECs offers potential therapeutic hints for enhancing mucosal immunity and treating related diseases affecting gastrointestinal health. This chapter explores the key cellular players of mucosal immunity and the importance of epithelial-T cell interactions for immune regulation and potential therapeutic applications.