<p>Inflammatory bowel disease (IBD) is chronic, relapsing, intestinal inflammation characterized by periods of remission and exacerbation. Pathogenesis of IBD is a complex process and the exact aetiology is unclear yet. Studies have provided evidences that IBD is a result of a genetic predisposition that leads to a mucosal immune regulatory cell defect, barrier defects, and susceptibility to environmental triggers like luminal bacteria and specific antigens. Innate and adaptive immune responses to commensal bacteria are balanced by the multiple regulatory cells like T regs and B regs. Monoclonal-antibody-based therapies have been identified for the treatment of IBD but, they have side effects and the efficacy is not stable. Hence, great expectations lie towards finding a successful cure for IBD.</p> <p>Recent studies have proved the involvement of several different genes in the pathogenesis of IBD and there expressions were highly reduced in IBD. Homeodomain only protein- Hopx is a nuclear protein required to modulate heart growth and function. Expression of Hopx has been reported in various types of normal tissues but not in malignant tissues. Recent study on Hopx revealed that Hopx is needed for the function of regulatory T cells induced by DCs. However the correlation between Hopx gene and IBD remains unanswered. In this study, we examined the role of Hopx expressing regulatory B cell in IBD.</p> <p>The aim of this study is to investigate whether the expression of Hopx in regulatory B cell play a key role in suppressing colitis in murine model.</p> <p>The expression of Hopx was studied using cellular and molecular techniques including flowcytometry, immunohistochemistry, western blotting and real time RT-PCR.</p> <p>As a first step, we investigated the Hopx expression in colitis and control murine model. After we found the possible involvement of Hopx gene in regulating intestinal inflammation, we further our study to investigate whether Hopx is expressed by regulatory B cell and function together to inhibit intestinal inflammation. After establishing Hopx and B regs association, we used probiotics to modulate Hopx expression in regulatory B cells in order to prevent/reduce intestinal inflammation. Finally we elucidate the importance of Hopx expression by injecting neutralizing anti-Hopx antibody to block Hopx.</p> <p>Together, studies on human intestinal tissue and murine model revealed that Hopx expression is suppressed during inflammation condition. Probiotic administration helps to increase Hopx expressing Breg cell thereby, prevent IBD. Hopx deficient group expressed high frequency of proinflammatory cytokines and reduced immune regulatory cells. This particular study proposes that the down regulation of Hopx contributes to the development of intestinal inflammation.</p> / Master of Health Sciences (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/12807 |
| Date | 04 1900 |
| Creators | Thayaparana, Nalayini |
| Contributors | Yang, Pingchang, Tang, Damu, Forsythe, Paul, Medical Sciences |
| Source Sets | McMaster University |
| Detected Language | English |
| Type | thesis |
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