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Role of CCL25/CCR9 in immune homeostasis and disease

Svensson, Marcus LU and Agace, William W. LU (2006) In Expert Review of Clinical Immunology 2(5). p.759-773
Abstract

Chemokines constitute a large family of low-molecular-weight proteins (∼10 kDa in size), recognized primarily for their role in directing leukocyte migration under both homeostatic and inflammatory settings. The chemokine CCL25 displays a unique and highly restricted expression pattern compared with other chemokine family members. In the steady state, CCL25 is expressed at high levels primarily in the thymus and small intestine, while its sole functional receptor, CCR9, is expressed on subsets of developing thymocytes and intestinal lymphocytes. Mice that are deficient in CCR9 show relatively normal thymocyte development; however, in competitive transfer experiments, CC99-/- bone-marrow cells are severely disadvantaged in... (More)

Chemokines constitute a large family of low-molecular-weight proteins (∼10 kDa in size), recognized primarily for their role in directing leukocyte migration under both homeostatic and inflammatory settings. The chemokine CCL25 displays a unique and highly restricted expression pattern compared with other chemokine family members. In the steady state, CCL25 is expressed at high levels primarily in the thymus and small intestine, while its sole functional receptor, CCR9, is expressed on subsets of developing thymocytes and intestinal lymphocytes. Mice that are deficient in CCR9 show relatively normal thymocyte development; however, in competitive transfer experiments, CC99-/- bone-marrow cells are severely disadvantaged in their ability to generate mature T cells compared with wildtype cells. Indeed, expression data and analysis of genetically modified mice suggest that CCL25/CCR9 may be involved in multiple stages of thymocyte development. Recent in vivo studies have demonstrated a role for CCL25/CCR9 in mediating lymphocyte recruitment to the small intestine and in the development of the small intestinal T-cell receptor-γδ T-cell compartment. Finally, CCL25 is expressed in the small intestine of Crohn's disease patients and, in certain inflammatory conditions, outside the small intestine. Together, these results suggest an important role for CCL25/CCR9 in T-cell development and small intestinal immunity and suggest that targeting the CCL25/CCR9 pathway may provide a means to modulate small intestinal immune responses.

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author
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organization
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type
Contribution to journal
publication status
published
subject
keywords
CCL25, CCR9, Chemokine, Chemokine receptor, Dendritic cell, Homing, Inflammatory bowel disease, Small intestine, T-cell development, Thymus
in
Expert Review of Clinical Immunology
volume
2
issue
5
pages
15 pages
publisher
Expert Reviews
external identifiers
  • scopus:84872589266
ISSN
1744-666X
DOI
10.1586/1744666X.2.5.759
language
English
LU publication?
yes
id
8084197e-49e8-45fb-aff8-482949235734
date added to LUP
2019-05-30 13:49:54
date last changed
2021-08-25 04:25:35
@article{8084197e-49e8-45fb-aff8-482949235734,
  abstract     = {<p>Chemokines constitute a large family of low-molecular-weight proteins (∼10 kDa in size), recognized primarily for their role in directing leukocyte migration under both homeostatic and inflammatory settings. The chemokine CCL25 displays a unique and highly restricted expression pattern compared with other chemokine family members. In the steady state, CCL25 is expressed at high levels primarily in the thymus and small intestine, while its sole functional receptor, CCR9, is expressed on subsets of developing thymocytes and intestinal lymphocytes. Mice that are deficient in CCR9 show relatively normal thymocyte development; however, in competitive transfer experiments, CC99<sup>-/-</sup> bone-marrow cells are severely disadvantaged in their ability to generate mature T cells compared with wildtype cells. Indeed, expression data and analysis of genetically modified mice suggest that CCL25/CCR9 may be involved in multiple stages of thymocyte development. Recent in vivo studies have demonstrated a role for CCL25/CCR9 in mediating lymphocyte recruitment to the small intestine and in the development of the small intestinal T-cell receptor-γδ T-cell compartment. Finally, CCL25 is expressed in the small intestine of Crohn's disease patients and, in certain inflammatory conditions, outside the small intestine. Together, these results suggest an important role for CCL25/CCR9 in T-cell development and small intestinal immunity and suggest that targeting the CCL25/CCR9 pathway may provide a means to modulate small intestinal immune responses.</p>},
  author       = {Svensson, Marcus and Agace, William W.},
  issn         = {1744-666X},
  language     = {eng},
  number       = {5},
  pages        = {759--773},
  publisher    = {Expert Reviews},
  series       = {Expert Review of Clinical Immunology},
  title        = {Role of CCL25/CCR9 in immune homeostasis and disease},
  url          = {http://dx.doi.org/10.1586/1744666X.2.5.759},
  doi          = {10.1586/1744666X.2.5.759},
  volume       = {2},
  year         = {2006},
}