Dissecting immune and stromal niches along the length of the human intestine
Abstract
The intestinal mucosa contains the most diverse and largest number of immune cells in the body. Immune cells in the intestine are localized within two main compartments. The first comprises the specialized lymphoid organs collectively known as gut-associated lymphoid tissues (GALT) which are the sites where adaptive immune responses are initiated, and the second is the connective tissue of the gut wall (the “lamina propria”) and epithelium where adaptive immune cells localize and carry out many of their functions. These two compartments contain different immune cells and carry out distinct functions, highlighting the importance of studying these structures independently. Most of the studies assessing the function of GALT have been performed in animal models and our understanding of the structure, immune composition and function of human GALT remains limited. In the current thesis we developed a novel technique to identify and isolate human GALT from surrounding intestinal tissue. We subsequently used these methods to assess the immune cell compartment of GALT and lamina propria free of GALT. Our results suggest a role for small GALT structures termed isolated lymphoid follicles in contributing to regional immune responses within the intestine. Effective immune responses require many different cell types to act in concert. Amongst these are the stromal cells (SCs) that are best known for providing the scaffolding that holds tissues together, but more recently implicated in the regulation of immune responses. In the second part of the project, we set out to better understand SCs in the intestine, using recently developed methods that allow genes to be analyzed in individual cells. In this way, we identified several distinct populations of SCs in the human small and large intestine and used the information to identify where they reside in the gut wall, as well as predict their possible functions. These populations included the SCs known as myofibroblasts that have been associated with inflammatory reactions and we found these to be more prevalent during intestinal inflammation. Together our results pave the way for more detailed analysis on the function of GALT and SC subsets in intestinal homeostasis and disease, potentially enabling the development of new treatments for inflammatory bowel disease such as Crohn’s disease and ulcerative colitis.
Info
Thesis PhD, 2019
UN SDG Classification
DK Main Research Area
Science/Technology
