Differential homing mechanisms regulate regionalized effector CD8 alpha beta(+) T cell accumulation within the small intestine
(2007) In Proceedings of the National Academy of Sciences 104(24). p.10122-10127- Abstract
- The CC chemokine receptor (CCR)9 is expressed on the majority of small intestinal, but few colonic, T cells, whereas its ligand CCL25 is constitutively expressed by small intestinal epithelial cells. As such, CCR9/CCL25 have been proposed to play a central role in regulating small intestinal but not colonic immune responses and thus to organize regionalized immunity within the intestinal mucosa. Here, we demonstrate that CCL25 is expressed at reduced levels by epithelial cells in the distal compared with proximal small intestine, which correlated with less efficient CCR9-dependent effector CD8 alpha ss(+) T cell entry into the ileal epithelium. In vitro-generated alpha(4)ss(+)(7) effector CD8 alpha ss(+) T cell entry into the lamina... (More)
- The CC chemokine receptor (CCR)9 is expressed on the majority of small intestinal, but few colonic, T cells, whereas its ligand CCL25 is constitutively expressed by small intestinal epithelial cells. As such, CCR9/CCL25 have been proposed to play a central role in regulating small intestinal but not colonic immune responses and thus to organize regionalized immunity within the intestinal mucosa. Here, we demonstrate that CCL25 is expressed at reduced levels by epithelial cells in the distal compared with proximal small intestine, which correlated with less efficient CCR9-dependent effector CD8 alpha ss(+) T cell entry into the ileal epithelium. In vitro-generated alpha(4)ss(+)(7) effector CD8 alpha ss(+) T cell entry into the lamina propria was less dependent on CCR9 than entry into the epithelium along the entire length of the small intestine and in particular in the ileum. CCR9-independent alpha(4)ss(+)(7) effector CD8 alpha ss(+) T cell entry was pertussis toxin-sensitive, suggesting a role for additional Gal-linked G protein-coupled receptors. Finally, in vivo-primed effector CD8 alpha ss(+) T cells displayed regionalized differences in their entry to the small intestinal epithelium with enhanced CCR9-independent entry to the ileum. These results highlight a hitherto underappreciated compartmentalization of immune responses within the small intestine and have direct implications for targeting strategies aimed at regulating T cell localization to the small intestinal mucosa. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/657673
- author
- Stenstad, Hanna LU ; Svensson Frej, Marcus LU ; Cucak, Helena LU ; Kotarsky, Knut LU and Agace, William LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- chemokine receptor, intestinal mucosa
- in
- Proceedings of the National Academy of Sciences
- volume
- 104
- issue
- 24
- pages
- 10122 - 10127
- publisher
- National Academy of Sciences
- external identifiers
-
- wos:000247363000038
- scopus:34547219103
- pmid:17551016
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.0700269104
- language
- English
- LU publication?
- yes
- id
- ff72a2a2-cf1d-4b66-ba03-242be1b6c0e7 (old id 657673)
- date added to LUP
- 2016-04-01 12:05:55
- date last changed
- 2022-03-13 05:17:28
@article{ff72a2a2-cf1d-4b66-ba03-242be1b6c0e7,
abstract = {{The CC chemokine receptor (CCR)9 is expressed on the majority of small intestinal, but few colonic, T cells, whereas its ligand CCL25 is constitutively expressed by small intestinal epithelial cells. As such, CCR9/CCL25 have been proposed to play a central role in regulating small intestinal but not colonic immune responses and thus to organize regionalized immunity within the intestinal mucosa. Here, we demonstrate that CCL25 is expressed at reduced levels by epithelial cells in the distal compared with proximal small intestine, which correlated with less efficient CCR9-dependent effector CD8 alpha ss(+) T cell entry into the ileal epithelium. In vitro-generated alpha(4)ss(+)(7) effector CD8 alpha ss(+) T cell entry into the lamina propria was less dependent on CCR9 than entry into the epithelium along the entire length of the small intestine and in particular in the ileum. CCR9-independent alpha(4)ss(+)(7) effector CD8 alpha ss(+) T cell entry was pertussis toxin-sensitive, suggesting a role for additional Gal-linked G protein-coupled receptors. Finally, in vivo-primed effector CD8 alpha ss(+) T cells displayed regionalized differences in their entry to the small intestinal epithelium with enhanced CCR9-independent entry to the ileum. These results highlight a hitherto underappreciated compartmentalization of immune responses within the small intestine and have direct implications for targeting strategies aimed at regulating T cell localization to the small intestinal mucosa.}},
author = {{Stenstad, Hanna and Svensson Frej, Marcus and Cucak, Helena and Kotarsky, Knut and Agace, William}},
issn = {{1091-6490}},
keywords = {{chemokine receptor; intestinal mucosa}},
language = {{eng}},
number = {{24}},
pages = {{10122--10127}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{Differential homing mechanisms regulate regionalized effector CD8 alpha beta(+) T cell accumulation within the small intestine}},
url = {{http://dx.doi.org/10.1073/pnas.0700269104}},
doi = {{10.1073/pnas.0700269104}},
volume = {{104}},
year = {{2007}},
}