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dc.contributor.authorLucchesi, Davide
dc.date.accessioned2015-09-09T11:54:16Z
dc.date.available2015-09-09T11:54:16Z
dc.date.issued2015-02-06
dc.identifier.citationLucchesi, D. 2015. 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. Queen Mary University of Londonen_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/8565
dc.descriptionPhDen_US
dc.description.abstractThe 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.en_US
dc.language.isoenen_US
dc.publisherQueen Mary University of Londonen_US
dc.subjectExperimental Medicine and Rheumatology.en_US
dc.subjectMedicineen_US
dc.subjecttertiary lymphoid structuresen_US
dc.subjectectopic lymphoid neogenesisen_US
dc.titleDevelopment and description of a novel inducible model of salivary gland inflammation in C57BL/6 mice characterised by tertiary lymphoid structures, autoimmunity and exocrine dysfunctionen_US
dc.typeThesisen_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author


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