Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.667392
Title: Development and description of a novel inducible model of salivary gland inflammation in C57BL/6 mice characterised by tertiary lymphoid structures, autoimmunity and exocrine dysfunction
Author: Lucchesi, Davide
ISNI:       0000 0004 5360 4270
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2015
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Abstract:
The accumulation of leukocytes in non-lymphoid tissues and their structural organization into tertiary lymphoid structures (TLS), a process known as ectopic lymphoid neogenesis (ELN), is observed in response to chronic inflammation and in the target organ of several autoimmune diseases. TLS strongly resemble secondary lymphoid organs with specialised high-endothelial venules (HEV), segregated B/T cell areas and presence of follicular dendritic cells (FDC) networks promoting in situ affinity maturation of the antibody response. TLS have been associated with a growing number of autoimmune conditions and usually their presence is prognostic for undesirable disease progression. In Sjögren’s syndrome (SS), an autoimmune disease affecting the salivary and lachrymal glands leading to exocrine dysfunction, TLS develop in the salivary glands (SG) of around one-third of the patients. The immunobiology of the SG and the pathogenesis of SS have been poorly clarified and to date a robust and reproducible inducible animal model of SS and TLS in the SG is still absent. In my PhD, I developed and validated a novel inducible model of ELN in murine SG that also reproduces several features of SS. The retrograde administration of a replication-deficient adenovirus (AdV) in the SGs of wild-type C57Bl/6 mice was able to induce within three weeks fully formed TLS that displayed B/T cell segregation, FDC networks, HEVs and were positive for markers of germinal centres. Moreover, the AdV-treated mice showed a significant reduction of salivary flow and in 75% of the cases development of anti-nuclear antibodies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.667392  DOI: Not available
Keywords: Experimental Medicine and Rheumatology. ; Medicine ; tertiary lymphoid structures ; ectopic lymphoid neogenesis
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