Abstract
The intestinal mucosa represents a unique environment where the coordinated function of diverse epithelial, mesenchymal, and immune cells maintains a physiologically balanced environment in the presence of gut microbiota. The intestinal mucosa plays a central role in the pathogenesis of inflammatory bowel disease (IBD), yet the molecular and cellular composition of this diverse environment is poorly understood. However, the recent advent of multimodal single-cell technologies, including single-cell RNA sequencing (scRNA-seq), now provides an opportunity to accurately map the tissue architecture, characterize rare cell types that were previously overlooked, and define function at a single-cell level. In this review, we summarize key advances in single-cell technology and provide an overview of important aspects of computational analysis. We describe emerging data in the field of IBD and discuss how the characterization of novel intestinal mucosa cell populations is reshaping our understanding of this complex disease. We conclude by considering the potential clinical applications, including the definition of novel drug targets and the opportunity for personalization of care in this exciting new era of precision medicine.
Highlights
The gastrointestinal mucosa is the largest immunological organ in the body and represents a uniquely challenging environment, where a careful balance must be maintained between tolerance and immune response in the presence of a huge bacterial burden
During their development in the thymus, T cells acquire the capacity to recognize foreign antigens through the expression of polymorphic T cell receptors (TCRs).[37]. These TCRs are composed of 2 glycoprotein chains; alpha (α) and beta (β) chains represent more than 90% of the total T cell population, while gamma (γ) and delta (δ)chains are a much smaller subset
This study demonstrated that persisting resident CD8+ T cells survive over 1 year in transplanted duodenum, and a limited number of expanded clones characterize the TCR repertoire of these cells
Summary
Daniele Corridoni, PhD,*,†, Thomas Chapman, MD, PhD,† Agne Antanaviciute, PhD,*,‡ Jack Satsangi, MD, PhD,† and Alison Simmons, MD, PhD*,†. The intestinal mucosa represents a unique environment where the coordinated function of diverse epithelial, mesenchymal, and immune cells maintains a physiologically balanced environment in the presence of gut microbiota. The intestinal mucosa plays a central role in the pathogenesis of inflammatory bowel disease (IBD), yet the molecular and cellular composition of this diverse environment is poorly understood. The recent advent of multimodal single-cell technologies, including single-cell RNA sequencing (scRNA-seq), provides an opportunity to accurately map the tissue architecture, characterize rare cell types that were previously overlooked, and define function at a single-cell level. We describe emerging data in the field of IBD and discuss how the characterization of novel intestinal mucosa cell populations is reshaping our understanding of this complex disease.
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