Involvement of CCR9 at multiple stages of adult T lymphopoiesis.
(2008) In Journal of Leukocyte Biology 83(1). p.156-164- Abstract
- The chemokine CCL25 is constitutively expressed in the thymus, and its receptor CCR9 is expressed on subsets of developing thymocytes. Nevertheless, the function of CCL25/CCR9 in adult thymopoiesis remains unclear. Here, we demonstrate that purified CCR9–/– hematopoietic stem cells are deficient in their ability to generate all major thymocyte subsets including double-negative 1 (DN1) cells in competitive transfers. CCR9–/– bone marrow contained normal numbers of lineage– Sca-1+c-kit+, common lymphoid progenitors, and lymphoid-primed multipotent progenitors (LMPP), and CCR9–/– LMPP showed similar T cell potential as their wild-type (WT) counterparts when cultured on OP9–{delta}-like 1 stromal cells. In contrast, early thymic progenitor and... (More)
- The chemokine CCL25 is constitutively expressed in the thymus, and its receptor CCR9 is expressed on subsets of developing thymocytes. Nevertheless, the function of CCL25/CCR9 in adult thymopoiesis remains unclear. Here, we demonstrate that purified CCR9–/– hematopoietic stem cells are deficient in their ability to generate all major thymocyte subsets including double-negative 1 (DN1) cells in competitive transfers. CCR9–/– bone marrow contained normal numbers of lineage– Sca-1+c-kit+, common lymphoid progenitors, and lymphoid-primed multipotent progenitors (LMPP), and CCR9–/– LMPP showed similar T cell potential as their wild-type (WT) counterparts when cultured on OP9–{delta}-like 1 stromal cells. In contrast, early thymic progenitor and DN2 thymocyte numbers were reduced in the thymus of adult CCR9–/– mice. In fetal thymic organ cultures (FTOC), CCR9–/– DN1 cells were as efficient as WT DN1 cells in generating double-positive (DP) thymocytes; however, under competitive FTOC, CCR9–/– DP cell numbers were reduced significantly. Similarly, following intrathymic injection into sublethally irradiated recipients, CCR9–/– DN cells were out-competed by WT DN cells in generating DP thymocytes. Finally, in competitive reaggregation thymic organ cultures, CCR9–/– preselection DP thymocytes were disadvantaged significantly in their ability to generate CD4 single-positive (SP) thymocytes, a finding that correlated with a reduced ability to form TCR-MHC-dependent conjugates with thymic epithelial cells. Together, these results highlight a role for CCR9 at several stages of adult thymopoiesis: in hematopoietic progenitor seeding of the thymus, in the DN-DP thymocyte transition, and in the generation of CD4 SP thymocytes. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/608778
- author
- Svensson Frej, Marcus LU ; Marsal, Jan LU ; Uronen-Hansson, Heli LU ; Cheng, Min LU ; Jenkinson, William ; Cilio, Corrado LU ; Jacobsen, Sten Eirik W LU ; Sitnicka Quinn, Ewa LU ; Anderson, Graham and Agace, William LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Leukocyte Biology
- volume
- 83
- issue
- 1
- pages
- 156 - 164
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000251834100019
- scopus:38149019947
- ISSN
- 1938-3673
- DOI
- 10.1189/jlb.0607423
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Stem Cell Center (013041110), Pediatrics/Urology/Gynecology/Endocrinology (013240400), Immunology (013212020), Cellular Autoimmunity Unit (013241520)
- id
- 36f2ea4b-4398-4908-a142-039a707c5b7a (old id 608778)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17911179&dopt=Abstract
- date added to LUP
- 2016-04-01 12:37:34
- date last changed
- 2022-08-06 20:43:27
@article{36f2ea4b-4398-4908-a142-039a707c5b7a,
abstract = {{The chemokine CCL25 is constitutively expressed in the thymus, and its receptor CCR9 is expressed on subsets of developing thymocytes. Nevertheless, the function of CCL25/CCR9 in adult thymopoiesis remains unclear. Here, we demonstrate that purified CCR9–/– hematopoietic stem cells are deficient in their ability to generate all major thymocyte subsets including double-negative 1 (DN1) cells in competitive transfers. CCR9–/– bone marrow contained normal numbers of lineage– Sca-1+c-kit+, common lymphoid progenitors, and lymphoid-primed multipotent progenitors (LMPP), and CCR9–/– LMPP showed similar T cell potential as their wild-type (WT) counterparts when cultured on OP9–{delta}-like 1 stromal cells. In contrast, early thymic progenitor and DN2 thymocyte numbers were reduced in the thymus of adult CCR9–/– mice. In fetal thymic organ cultures (FTOC), CCR9–/– DN1 cells were as efficient as WT DN1 cells in generating double-positive (DP) thymocytes; however, under competitive FTOC, CCR9–/– DP cell numbers were reduced significantly. Similarly, following intrathymic injection into sublethally irradiated recipients, CCR9–/– DN cells were out-competed by WT DN cells in generating DP thymocytes. Finally, in competitive reaggregation thymic organ cultures, CCR9–/– preselection DP thymocytes were disadvantaged significantly in their ability to generate CD4 single-positive (SP) thymocytes, a finding that correlated with a reduced ability to form TCR-MHC-dependent conjugates with thymic epithelial cells. Together, these results highlight a role for CCR9 at several stages of adult thymopoiesis: in hematopoietic progenitor seeding of the thymus, in the DN-DP thymocyte transition, and in the generation of CD4 SP thymocytes.}},
author = {{Svensson Frej, Marcus and Marsal, Jan and Uronen-Hansson, Heli and Cheng, Min and Jenkinson, William and Cilio, Corrado and Jacobsen, Sten Eirik W and Sitnicka Quinn, Ewa and Anderson, Graham and Agace, William}},
issn = {{1938-3673}},
language = {{eng}},
number = {{1}},
pages = {{156--164}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Leukocyte Biology}},
title = {{Involvement of CCR9 at multiple stages of adult T lymphopoiesis.}},
url = {{http://dx.doi.org/10.1189/jlb.0607423}},
doi = {{10.1189/jlb.0607423}},
volume = {{83}},
year = {{2008}},
}