McNamee, Eóin N. and Masterson, Joanne C. and Jedlicka, Paul and Collins, Colm B. and Williams, Ifor R. and Rivera-Nieves, Jesus
(2013)
Ectopic lymphoid tissue alters the chemokine
gradient, increases lymphocyte retention and
exacerbates murine ileitis.
Gut, 62 (1).
pp. 53-62.
ISSN 1468-3288
Abstract
Background The earliest endoscopically-evident lesion in
Crohn’s disease is the aphthous ulcer, which develops
over ectopic lymphoid tissues (ie, inducible lymphoid
follicles (ILF), tertiary lymphoid tissue (TLT)) in the
chronically inflamed intestine. ILF/TLT are induced within
effector sites by homeostatic lymphoid chemokines, but
their role in the development of intestinal ILF/TLT and in
the pathogenesis of Crohn’s disease is poorly understood.
Design Using a mouse model of Crohn’s-like ileitis
(TNFΔARE) which develops florid induction of ILF/TLT
within its terminal ileum, the contribution of the CCR7/
CCL19/CCL21 chemokine axis during the development of
TLT and its role in disease pathogenesis were assessed.
Results Both CCL19 and CCL21 were increased within
the inflamed ileum of TNFΔARE mice, which resulted in
CCR7 internalisation and impaired T cell chemotaxis. ILF/
TLT were a major source of CCL19 and CCL21 and
increased local synthesis, augmented recruitment/
retention of effector, naı¨ve and central memory T cell
subsets within the inflamed ileum. Immunoblockade of
CCR7 resulted in further effector T cell retention and
exacerbation of ileitis.
Conclusions Induction of ILF/TLT in the chronically
inflamed intestine alters the homeostatic CCL19-CCL21
lymphoid-chemokine gradient and increases recruitment/
retention of effector CCR7+ T cell subsets within the
terminal ileum, contributing to the perpetuation of
chronic inflammation. Thus, blockade of CCR7 or its
ligands might result in deleterious consequences for
subjects with chronic inflammatory diseases.
| Item Type: |
Article
|
| Keywords: |
Ectopic; lymphoid tissue; alters; chemokine
gradient; increases lymphocyte retention;
exacerbates; murine ileitis; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
12489 |
| Identification Number: |
https://doi.org/10.1136/gutjnl-2011-301272 |
| Depositing User: |
Joanne Masterson
|
| Date Deposited: |
27 Feb 2020 14:29 |
| Journal or Publication Title: |
Gut |
| Publisher: |
BMJ Publishing Group |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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