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Expression and regulation of CCL25 and its role in T cell localization to and function within the small intestine

Ericsson, Anna LU (2005)
Abstract
Earlier studies have demonstrated an important role for the chemokine CCL25, and its receptor CCR9, in the generation of the small intestinal lymphocyte compartment. The work in this thesis was aimed at determining how CCL25 is regulated within the small intestinal mucosa, and what potential role it plays in T cell localization to and function within this site. We have identified epithelial cells as the main source of CCL25 mRNA in the small intestine, and also defined the CCL25 minimal promotor. CCL25 expression was independent of signaling through the lymphotoxin b receptor (LTbR) and inflammatory stimuli, which are signals regulating other chemokine genes. Instead, we suggest a novel role for the caudal related homeobox transcription... (More)
Earlier studies have demonstrated an important role for the chemokine CCL25, and its receptor CCR9, in the generation of the small intestinal lymphocyte compartment. The work in this thesis was aimed at determining how CCL25 is regulated within the small intestinal mucosa, and what potential role it plays in T cell localization to and function within this site. We have identified epithelial cells as the main source of CCL25 mRNA in the small intestine, and also defined the CCL25 minimal promotor. CCL25 expression was independent of signaling through the lymphotoxin b receptor (LTbR) and inflammatory stimuli, which are signals regulating other chemokine genes. Instead, we suggest a novel role for the caudal related homeobox transcription factors Cdx-1 and Cdx-2 in driving small intestinal CCL25 expression. We have also showed that CCL25 promotes the induction and function of the integrin CD103 on small intestinal IEL. CD103 interacts with E-cadherin on epithelial cells, and by modulating this interaction CCL25 may regulate IEL-epithelial cell interactions and thus have effects on both IEL and epithelial cell function in the small intestine.



Finally, we examined the role of CCL25/CCR9 in CD4 T cell localization to the small intestinal lamina propria and demonstrate both CCR9 dependent and independent mechanisms for CD4 T cell entry into the this site. (Less)
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author
supervisor
opponent
  • Professor Moser, Bernard, Theodor-Kocher Institute, University of Bern, Bern, Switzerland
organization
publishing date
type
Thesis
publication status
published
subject
keywords
mucosa, epithelium, intestine, transplantation, serology, Immunologi, Immunology, integrin, serologi, Chemokine
pages
157 pages
publisher
Lund University, Faculty of Medicine
defense location
GK-salen BMC Sölvegatan 19 Lund
defense date
2005-04-28 09:00
ISSN
1652-8220
ISBN
91-85439-22-3
language
English
LU publication?
yes
id
59849c11-8722-4d6e-804b-871e1b9afa36 (old id 544672)
date added to LUP
2007-09-11 14:19:28
date last changed
2016-09-19 08:44:53
@phdthesis{59849c11-8722-4d6e-804b-871e1b9afa36,
  abstract     = {Earlier studies have demonstrated an important role for the chemokine CCL25, and its receptor CCR9, in the generation of the small intestinal lymphocyte compartment. The work in this thesis was aimed at determining how CCL25 is regulated within the small intestinal mucosa, and what potential role it plays in T cell localization to and function within this site. We have identified epithelial cells as the main source of CCL25 mRNA in the small intestine, and also defined the CCL25 minimal promotor. CCL25 expression was independent of signaling through the lymphotoxin b receptor (LTbR) and inflammatory stimuli, which are signals regulating other chemokine genes. Instead, we suggest a novel role for the caudal related homeobox transcription factors Cdx-1 and Cdx-2 in driving small intestinal CCL25 expression. We have also showed that CCL25 promotes the induction and function of the integrin CD103 on small intestinal IEL. CD103 interacts with E-cadherin on epithelial cells, and by modulating this interaction CCL25 may regulate IEL-epithelial cell interactions and thus have effects on both IEL and epithelial cell function in the small intestine.<br/><br>
<br/><br>
Finally, we examined the role of CCL25/CCR9 in CD4 T cell localization to the small intestinal lamina propria and demonstrate both CCR9 dependent and independent mechanisms for CD4 T cell entry into the this site.},
  author       = {Ericsson, Anna},
  isbn         = {91-85439-22-3},
  issn         = {1652-8220},
  keyword      = {mucosa,epithelium,intestine,transplantation,serology,Immunologi,Immunology,integrin,serologi,Chemokine},
  language     = {eng},
  pages        = {157},
  publisher    = {Lund University, Faculty of Medicine},
  school       = {Lund University},
  title        = {Expression and regulation of CCL25 and its role in T cell localization to and function within the small intestine},
  year         = {2005},
}