The role of gut tissue in arthritis: unravelling glycomic and inflammatory networks underlying immunoregulation

Pan, Piaopiao (2024) The role of gut tissue in arthritis: unravelling glycomic and inflammatory networks underlying immunoregulation. PhD thesis, University of Glasgow.

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune chronic disease, which affects not only joints, but skin, lungs, and heart as well. The pathogenesis of RA is complex and is not fully understood yet. Extensive research has focused on RA treatment, and induction of oral tolerance may be a promising therapeutic strategy. Collagen-derived products have been used to induce oral tolerance and undenatured type II collagen (UC-II), which preserves the physiological structure of collagen fibres, has shown an enhanced ability to induce tolerance, although its protective mechanism is not yet fully understood.

The intestinal mucosal site is a dynamic and multifunctional interface that is essential for nutrient absorption, immunological defence, microbiota interaction, and overall digestive and metabolic health. Its proper function is vital for maintaining overall well-being and preventing various gastrointestinal disorders. Recent studies found that dysbiosis at the intestinal mucosal site is associated with RA onset. Most research on the mucosal therapeutic potential in RA has focused on the modulation of immune and tolerogenic responses in the gut, while less attention has been given to stromal cells within the local microenvironment.

Glycans, covering all cell membranes, are pivotal to a wide range of biological functions including cell communication, cell adhesion, and cell signalling. They are a hidden player in the immunological regulation of health and inflammation. The role of glycosylation in intestinal homeostasis and microbial composition has increasingly gained attention over the past few years. Alterations in glycosylation have been observed in many intestinal diseases. However, whether glycosylation profiles in the gut change in RA remains unknown. There are still many gaps in our understanding of gut pathology and of how intestinal glycosylation may affect oral tolerance during RA.

In this study, we thus, hypothesized that the protective effects of UC-II are associated not only with the induction of oral tolerance but also with the restoration of gut tissue integrity. Here, we used the mouse Collagen-Induced Arthritis (CIA) model as a surrogate for RA and investigated UC-II-mediated protective mechanisms, combined with transcriptomic and glycomic analysis of gut tissue including stromal cells to explore the glycan-related pathways. Overall, this work highlights the role of gut tissue in experimental arthritis, aiming to understand glycomic and inflammatory networks underlying oral tolerance induction by UC-II. This study will pave the way for novel therapeutic interventions targeting glycosylation/microbiota-related pathways in RA.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Supported by funding from Lonza Consumer Health Inc. and the University of Glasgow.
• Subjects: Q Science > QR Microbiology > QR180 Immunology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Supervisor's Name: Pineda, Dr. Miguel, Milling, Professor Simon and Harnett, Professor Margaret
• Date of Award: 2024
• Depositing User: Theses Team
• Unique ID: glathesis:2024-84184
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 02 Apr 2024 14:47
• Last Modified: 27 Feb 2026 10:03
• Thesis DOI: 10.5525/gla.thesis.84184
• URI: https://theses.gla.ac.uk/id/eprint/84184