title: The atypical chemokine receptor CCRL1 shapes functional CCL21 gradients in lymph nodes.
abstract: Afferent lymph-borne dendritic cells essentially rely on the chemokine receptor CCR7 for their transition from the subcapsular lymph node sinus into the parenchyma, a migratory step driven by putative gradients of CCR7 ligands. We found that lymph node fringes indeed contained physiological gradients of the chemokine CCL21, which depended on the expression of CCRL1, the atypical receptor for the CCR7 ligands CCL19 and CCL21. Lymphatic endothelial cells lining the ceiling of the subcapsular sinus, but not those lining the floor, expressed CCRL1, which scavenged chemokines from the sinus lumen. This created chemokine gradients across the sinus floor and enabled the emigration of dendritic cells. In vitro live imaging revealed that spatially confined expression of CCRL1 was necessary and sufficient for the creation of functional chemokine gradients.
authors.affiliation: 1] MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, UK. [2] [3].
authors.forename: Maria H
authors.initials: MH
authors.lastname: Ulvmar
authors.affiliation: 1] Institute of Immunology, Hannover Medical School, Hannover, Germany. [2].
authors.forename: Kathrin
authors.initials: K
authors.lastname: Werth
authors.affiliation: 1] Institute of Immunology, Hannover Medical School, Hannover, Germany. [2].
authors.forename: Asolina
authors.initials: A
authors.lastname: Braun
authors.affiliation: MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Poonam
authors.initials: P
authors.lastname: Kelay
authors.affiliation: MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Elin
authors.initials: E
authors.lastname: Hub
authors.affiliation: 1] MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, UK. [2] Division of Nephrology, Medical University of Graz, Graz, Austria.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Eller
authors.affiliation: MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Li
authors.initials: L
authors.lastname: Chan
authors.affiliation: MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Beth
authors.initials: B
authors.lastname: Lucas
authors.affiliation: MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Igor
authors.initials: I
authors.lastname: Novitzky-Basso
authors.affiliation: MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Institute of Laboratory Animal Science, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Thomas
authors.identifier: 0000000221219496
authors.initials: T
authors.lastname: Rülicke
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Robert J B
authors.initials: RJ
authors.lastname: Nibbs
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Worbs
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.affiliation: MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Antal
authors.initials: A
authors.lastname: Rot
mesh_terms: D000818:Animals; D002465:Cell Movement; D054421:Chemokine CCL21 / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D054388:Receptors, CCR / Q000502:physiology*
chemical_list: D054421:Chemokine CCL21; D054388:Receptors, CCR