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The atypical chemokine receptor CCRL1 shapes functional CCL21 gradients in lymph nodes
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The atypical chemokine receptor CCRL1 shapes functional CCL21 gradients in lymph nodes
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Journal Article
The atypical chemokine receptor CCRL1 shapes functional CCL21 gradients in lymph nodes
2014
Overview
Antigen-bearing dendritic cells transit through the lymphatics via chemokine receptor CCR7–dependent chemotactic cues. Rot and colleagues show that the atypical chemokine receptor CCRL1 establishes chemokine polarity in the subscapsular sinus that enables entry into the lymph node.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 14/1
/ 14/19
/ 14/34
/ 14/35
/ 14/63
/ Animals
/ Chemokine CCL21 - physiology
/ Dendritic Cells - physiology
/ Mice
