Elucidation of the mesenchymal LTβR role during tertiary lymphoid organ development and intestinal inflammation

Postgraduate Thesis uoadl:2782838 362 Read counter

Unit:
Specialty Molecular Biomedicine Mechanisms of Disease, Molecular and Cellular Therapies, and Bioinnovation
Library of the School of Health Sciences
Deposit date:
2018-09-11
Year:
2018
Author:
Iliopoulou Lida-Evangelia
Supervisors info:
Γεώργιος Κόλλιας, Καθηγητής, Ιατρικής, ΕΚΠΑ
Μαριέττα Αρμακά, Ερευνήτρια Γ, Τμήμα Ανοσολογίας, 'Ερευνητικό Κέντρο Βιοϊατρικών Επιστημών "Αλέξανδρος Φλέμινγκ"
Βασιλική Κολιαράκη, Ερευνήτρια Γ, Τμήμα Ανοσολογίας, 'Ερευνητικό Κέντρο Βιοϊατρικών Επιστημών "Αλέξανδρος Φλέμινγκ"
Original Title:
Elucidation of the mesenchymal LTβR role during tertiary lymphoid organ development and intestinal inflammation
Languages:
English
Translated title:
Elucidation of the mesenchymal LTβR role during tertiary lymphoid organ development and intestinal inflammation
Summary:
The intestinal tertiary lymphoid organs (TLOs), commonly known as ILFs, are B-cell clusters located in the lamina propria, important for IgA production. They have been found increased in IBD patients, but their actual role during disease is still unknown. Lymphotoxin beta receptor (LTβR) expressed by mesenchymal cells (MCs) has been reported as necessary for TLO development. Here, we aimed to identify the cellular requirements for ILF formations as well as their functions during disease progression in TNFΔΑRΕ mice, a spontaneous murine model of IBD. MC-specific LTβR deficient mice did not show alterations in the ILF number but the ILF-MC network was impaired. This finding revealed the importance of MC-LTβR for ILF organization both in health and disease. Since these mice still developed ILFs, we generated LTβR deficient mice that lack ILFs, to study their importance during inflammation. LTβR deletion in TNFΔΑRΕ mice did not affect the disease progression in the terminal ileum, suggesting that ILFs don't participate in the pathogenesis of this model. Interestingly, these mice developed inflammatory colitis characterized by submucosal immune infiltration, indicating an LTβR-dependent anti-inflammatory mechanism that acts specifically in the colon. Collectively, our results suggest that MC-specific LTβR facilitate the proper ILF organization and reveal a protective role for LTβR under colonic inflammatory conditions.
Main subject category:
Health Sciences
Keywords:
Iintestinal inflammation, LTbR, Tertiary lymhoid organs, Isolated lymphoid follicles, Mesenchymal cells
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
134
Number of pages:
45
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