CCRL1/ACKR4 is expressed in key thymic microenvironments but is dispensable for T lymphopoiesis at steady state in adult mice |
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| Authors: | Beth Lucas Andrea J. White Maria H. Ulvmar Robert J. B. Nibbs Katarzyna M. Sitnik William W. Agace William E. Jenkinson Graham Anderson Antal Rot |
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| Affiliation: | 1. MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Edgbaston, Birmingham, UK;2. Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden;3. Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK;4. Immunology Section, Department of Experimental Medical Science, Lund University, Lund, Sweden;5. Section of Immunology and Vaccinology, Danish Technical University Veterinary Institute, Copenhagen, Denmark;6. Department of Biology, Centre for Immunology and Infection, University of York, York, UK |
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| 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‐IIlowCD40? 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. |
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| Keywords: | ACKR4 CCRL1 Chemokines T‐cell development Thymic epithelial cells |
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