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.

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@article{13f8a602a7654c1e95f161d06912f02e,
title = "CCRL1/ACKR4 is expressed in key thymic microenvironments but is dispensable for T lymphopoiesis at steady state in adult mice",
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 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.",
keywords = "Animals, Antigens, CD40, Cell Differentiation, Cell Movement, Cellular Microenvironment, Epithelial Cells, Female, Gene Expression Regulation, Developmental, Lymphopoiesis, Male, Membrane Glycoproteins, Mice, Mice, Knockout, Pericytes, Receptors, CCR, Receptors, CCR7, Signal Transduction, Stem Cells, Stromal Cells, Thymocytes, Thymus Gland",
author = "Beth Lucas and White, {Andrea J} and Ulvmar, {Maria H} and Nibbs, {Robert J B} and Sitnik, {Katarzyna M} and Agace, {William W} and William Jenkinson and Graham Anderson and Antal Rot",
note = "{\textcopyright} 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2015",
month = feb,
doi = "10.1002/eji.201445015",
language = "English",
volume = "45",
pages = "574--83",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "2",

}

RIS

TY - JOUR

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 -