Location-specific regulation of intestinal lymphocyte frequency and function during homeostasis and intestinal inflammation

Abstract

The intestinal immune system maintains a delicate balance between defending against pathogens and preventing excessive inflammation. Immune cell function within the gastrointestinal tract is highly location-specific. Regulatory T cells (Tregs) play a critical role in maintaining immune tolerance and preventing autoimmunity, with dysfunction in these cells implicated in conditions such as inflammatory bowel disease (IBD). This thesis reviews the role and regulation of intestinal Treg cells and investigates the impact of the pro-inflammatory cytokine interleukin-23 (IL-23) on Treg cell function in homeostasis, intestinal inflammation, and cancer. Treg cells are uniquely sensitive to low-dose IL-2 due to their expression of the high-affinity IL-2 receptor, and the mechanisms underlying low-dose IL-2-mediated expansion of Treg cells are explored in humanized mice. Additionally, the thesis includes research on eosinophilic esophagitis (EoE), a chronic inflammatory condition characterized by eosinophil accumulation in the esophagus. Through high-throughput sequencing of patient biopsies, a comprehensive analysis of the EoE transcriptome is conducted, identifying novel cellular targets and advancing the understanding of EoE pathophysiology. Altogether, these findings contribute to a more nuanced understanding of intestinal immune regulation and offer insights that may guide the development of targeted therapies for chronic inflammatory and autoimmune diseases.