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CCRL1/ACKR4 is expressed in key thymic microenvironments but is dispensable for T lymphopoiesis at steady state in adult mice

Lucas, Beth; White, Andrea J.; Ulvmar, Maria H.; Nibbs, Robert J. B.; Sitnik, Katarzyna LU ; Agace, William LU ; Jenkinson, William E.; Anderson, Graham and Rot, Antal (2015) In European Journal of Immunology 45(2). p.574-583
Abstract
Thymus colonisation and thymocyte positioning are regulated by interactions between CCR7 and CCR9, and their respective ligands, CCL19/CCL21 and CCL25. The ligands of CCR7 and CCR9 also interact with the atypical receptor CCRL1 (also known as ACKR4), which is expressed in the thymus and has recently been reported to play an important role in normal alpha beta T-cell development. Here, we show that CCRL1 is expressed within the thymic cortex, predominantly by MHC-II(low)CD40(-) cortical thymic epithelial cells and at the subcapsular zone by a population of podoplanin(+) thymic epithelial cells in mice. Interestingly, CCRL1 is also expressed by stromal cells which surround the pericytes of vessels at the corticomedullary junction, the site... (More)
Thymus colonisation and thymocyte positioning are regulated by interactions between CCR7 and CCR9, and their respective ligands, CCL19/CCL21 and CCL25. The ligands of CCR7 and CCR9 also interact with the atypical receptor CCRL1 (also known as ACKR4), which is expressed in the thymus and has recently been reported to play an important role in normal alpha beta T-cell development. Here, we show that CCRL1 is expressed within the thymic cortex, predominantly by MHC-II(low)CD40(-) cortical thymic epithelial cells and at the subcapsular zone by a population of podoplanin(+) thymic epithelial cells in mice. Interestingly, CCRL1 is also expressed by stromal cells which surround the pericytes of vessels at the corticomedullary junction, the site for progenitor cell entry and mature thymocyte egress from the thymus. We show that CCRL1 suppresses thymocyte progenitor entry into the thymus, however, the thymus size and cellularity are the same in adult WT and CCRL1(-/-) mice. Moreover, CCRL1(-/-) mice have no major perturbations in T-cell populations at different stages of thymic differentiation and development, and have a similar rate of thymocyte migration into the blood. Collectively, our findings argue against a major role for CCRL1 in normal thymus development and function. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ACKR4, CCRL1, Chemokines, T-cell development, Thymic epithelial cells
in
European Journal of Immunology
volume
45
issue
2
pages
574 - 583
publisher
John Wiley & Sons
external identifiers
  • wos:000349625400026
  • scopus:84923081542
ISSN
1521-4141
DOI
10.1002/eji.201445015
language
English
LU publication?
yes
id
5e05f367-4712-4395-930e-71401b656649 (old id 5160226)
date added to LUP
2015-04-01 07:39:57
date last changed
2017-05-21 03:11:31
@article{5e05f367-4712-4395-930e-71401b656649,
  abstract     = {Thymus colonisation and thymocyte positioning are regulated by interactions between CCR7 and CCR9, and their respective ligands, CCL19/CCL21 and CCL25. The ligands of CCR7 and CCR9 also interact with the atypical receptor CCRL1 (also known as ACKR4), which is expressed in the thymus and has recently been reported to play an important role in normal alpha beta T-cell development. Here, we show that CCRL1 is expressed within the thymic cortex, predominantly by MHC-II(low)CD40(-) cortical thymic epithelial cells and at the subcapsular zone by a population of podoplanin(+) thymic epithelial cells in mice. Interestingly, CCRL1 is also expressed by stromal cells which surround the pericytes of vessels at the corticomedullary junction, the site for progenitor cell entry and mature thymocyte egress from the thymus. We show that CCRL1 suppresses thymocyte progenitor entry into the thymus, however, the thymus size and cellularity are the same in adult WT and CCRL1(-/-) mice. Moreover, CCRL1(-/-) mice have no major perturbations in T-cell populations at different stages of thymic differentiation and development, and have a similar rate of thymocyte migration into the blood. Collectively, our findings argue against a major role for CCRL1 in normal thymus development and function.},
  author       = {Lucas, Beth and White, Andrea J. and Ulvmar, Maria H. and Nibbs, Robert J. B. and Sitnik, Katarzyna and Agace, William and Jenkinson, William E. and Anderson, Graham and Rot, Antal},
  issn         = {1521-4141},
  keyword      = {ACKR4,CCRL1,Chemokines,T-cell development,Thymic epithelial cells},
  language     = {eng},
  number       = {2},
  pages        = {574--583},
  publisher    = {John Wiley & Sons},
  series       = {European Journal of Immunology},
  title        = {CCRL1/ACKR4 is expressed in key thymic microenvironments but is dispensable for T lymphopoiesis at steady state in adult mice},
  url          = {http://dx.doi.org/10.1002/eji.201445015},
  volume       = {45},
  year         = {2015},
}