Thesis
Mast cells and their role in rheumatoid arthritis
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2015
- Thesis identifier
- T14031
- Person Identifier (Local)
- 201391104
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Mast cells are active participants in tissue damage in autoimmune diseases, such as rheumatoid arthritis. Mast cells reside in connective tissues and the synovial tissue of joints, where they can produce pro-inflammatory mediators, proteases and cytokines. TNF-α is a cytokine produced by mast cells, and has been identified as key cytokine in the pathogenesis of rheumatoid arthritis. In the current study, we demonstrate the role of mast cells in the initiation and perpetuation of inflammatory arthritis, and their role as effector cells in this process. Using two mast cell-deficient mouse strains, KitWsh/Wsh mice and Mas-TRECK mice, investigation was conducted in an antibody induced model of arthritis, Collagen-Antibody Induced Arthritis (CAIA), and in a breach of tolerance model in arthritis. Investigation was also conducted into mast cell-dendritic cell interactions. Unlike previous studies it was found that the presence of mast cells in a model of CAIA was protective. Female Mas-TRECK positive mice, which lack mast cells, experienced significantly higher levels of arthritis-like symptoms, such as weight loss (p<0.05), paw swelling (p<0.05) and pathology (p<0.05), and higher levels of inflammatory cytokines compared to the Mas-TRECK negative mast cell competent mice, in an extended study. Contrary to the observed findings in the CAIA model, mast cells were found to be pathogenic in a breach of tolerance model of arthritis. In both KitWsh/Wsh mice and Mas-TRECK positive mice, arthritis-like symptoms were similar to those observed in the wild type mice. However, significantly higher levels of auto-antibody production (p<0.05) were found in the KitWsh/Wsh mice compared to the WT mice. Therefore, mast cells may be required for the induction of the breach of tolerance, but their pathogenesis ameliorates, and become regulatory in the later stages of arthritis. This study concludes that mast cells may play a role in pathogenesis of inflammatory arthritis. Mast cells may play a different role in the various stages of the disease, having a detrimental role in the induction phase leading to early inflammation and breach in tolerance, whereas in the latter chronic stages they may have an amelioratory role. Therefore this demonstrates their diverse ability as effector cells of the immune system.
- Resource Type
- DOI
- Date Created
- 2015
- Former identifier
- 1231335
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