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
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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.
Authors
Lucchesi, DavideCollections
- Theses [4223]