CCRL1/ACKR4 is expressed in key thymic microenvironments but is dispensable for T lymphopoiesis at steady state in adult mice
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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 M; Agace, William W; Jenkinson, William; Anderson, Graham; Rot, Antal.
In: European Journal of Immunology, Vol. 45, No. 2, 02.2015, p. 574-83.Research output: Contribution to journal › Article › peer-review
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T1 - CCRL1/ACKR4 is expressed in key thymic microenvironments but is dispensable for T lymphopoiesis at steady state in adult mice
AU - Lucas, Beth
AU - White, Andrea J
AU - Ulvmar, Maria H
AU - Nibbs, Robert J B
AU - Sitnik, Katarzyna M
AU - Agace, William W
AU - Jenkinson, William
AU - Anderson, Graham
AU - Rot, Antal
N1 - © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/2
Y1 - 2015/2
N2 - 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 αβT-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.
AB - 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 αβT-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.
KW - Animals
KW - Antigens, CD40
KW - Cell Differentiation
KW - Cell Movement
KW - Cellular Microenvironment
KW - Epithelial Cells
KW - Female
KW - Gene Expression Regulation, Developmental
KW - Lymphopoiesis
KW - Male
KW - Membrane Glycoproteins
KW - Mice
KW - Mice, Knockout
KW - Pericytes
KW - Receptors, CCR
KW - Receptors, CCR7
KW - Signal Transduction
KW - Stem Cells
KW - Stromal Cells
KW - Thymocytes
KW - Thymus Gland
U2 - 10.1002/eji.201445015
DO - 10.1002/eji.201445015
M3 - Article
C2 - 25521433
VL - 45
SP - 574
EP - 583
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 2
ER -