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.
authors.affiliation: MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: Beth
authors.initials: B
authors.lastname: Lucas
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: White
authors.forename: Maria H
authors.initials: MH
authors.lastname: Ulvmar
authors.forename: Robert J B
authors.initials: RJ
authors.lastname: Nibbs
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Sitnik
authors.forename: William W
authors.initials: WW
authors.lastname: Agace
authors.forename: William E
authors.initials: WE
authors.lastname: Jenkinson
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
authors.forename: Antal
authors.initials: A
authors.lastname: Rot
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D002465:Cell Movement; D060833:Cellular Microenvironment; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D038041:Lymphopoiesis / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020286:Pericytes / Q000166:cytology / Q000276:immunology; D054388:Receptors, CCR / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D060168:Thymocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000276:immunology / Q000378:metabolism*; D000098853:Podoplanin
chemical_list: D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D054388:Receptors, CCR; D054400:Receptors, CCR7; C000593439:Ackr4 protein, mouse; C119309:CC chemokine receptor 9; C515371:Ccr7 protein, mouse; C490441:Pdpn protein, mouse; D000098853:Podoplanin
keywords: ACKR4; CCRL1; Chemokines; T-cell development; Thymic epithelial cells