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Identifier |
000388608 |
Title |
Μελέτη της εμπλοκής της κυτοκίνης οστεοποντίνης στην έναρξη και ανάπτυξη της εντερικής φλεγμονής |
Alternative Title |
Study of the role of cytokine osteopontin in the initiation and development of intestinal inflammation |
Author
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Κουρεπίνη, Ευαγγελία
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Thesis advisor
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Τσατσάνης, Χ.
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Reviewer
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Πανουτσακοπούλου, Β.
Παπαδάκη, Ε.
Ηλιόπουλος, Α.
Καρδάσης, Δ.
Σουρβίνος, Γ.
Σιδηρόπουλος, Π.
|
Abstract |
Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative
colitis (UC), are caused by excessive inflammatory responses against commensal flora
and other antigens present in the intestinal lumen. Alternations in intestinal dendritic
cells (DCs) contribute to IBD development on humans and mice with experimental
colitis (EC). Mesenteric lymph node (MLN) DCs are crucial mediators of colitis
induction and they are separated in two main subsets that differentially express the
integrin αΕ (CD103): CD11chighCD103+ and CD11chighCD103- DCs. Although both
DC subsets are identified in MLNs during acute colitis, which DC subset mediates
colitis initiation remains unknown.
A recent study suggested the pro-inflammatory role for the cytokine osteopontin
(Opn) in chronic EC. In addition, Opn is highly expressed in intestinal immune and
non-immune mucosal cells, and in the plasma of IBD patients, as well as in colon and
plasma of mice with EC. Opn expressed by DCs during autoimmunity contributes to
the cellular mechanisms that mediate autoimmune diseases. Overall, Opn plays a role
in modulating DC phenotype, recruitment and function during several inflammatory
conditions. However, whether the crucial DC subset for colitis expresses Opn and the
possible significance of DC-expressed Opn is unknown.
The initial scope of this thesis was aimed in the identification of the critical DC subset
for acute colitis induction. We found that the MLN CD103- DCs exhibit proinflammatory
role in acute colitis. We address that apart from other inflammatory
cytokines, CD103- DCs expressed very high levels of Opn during colitis. We also
10
found that Opn expression by CD103- DCs is critical for their inflammatory
properties.
By different experimental approaches, this thesis addresses that Opn expression by
CD103- DCs could be solely responsible for their pro-inflammatory function. Thus,
here we demonstrate for the first time that particularly Opn expression by CD103-
DCs is crucial for their pro-inflammatory cytokine secretion. Opn expression boosted
the special capability of CD103- DCs to drive type 1 CD4 T-helper cell (Th1) and
Th17 cell polarization that mediate colitis. Additionally this thesis proposes a novel
targeted therapeutic approach for colitis. Particularly, we show that neutralization of
alpha 9 integrin that is a ligand for Opn, and is expressed specifically on CD103- DCs
surface during colitis, blocked the pro-inflammatory action of Opn.
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Language |
English |
Subject |
Alfa 9 integrin |
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Colitis |
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Dendritic cell |
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Osteopontin |
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¨Αλφα 9 ιντεγκρίνη |
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Δενδριτικό κύτταρο |
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Κολίτιδα |
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Οστεοποντίνη |
Issue date |
2014-07-24 |
Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/c/4/2/metadata-dlib-1416389558-10950-25447.tkl
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Views |
241 |