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The atypical chemokine receptor CCRL1 shapes functional CCL21 gradients in lymph nodes

Research output: Contribution to journalArticlepeer-review

Author(s)

  • Maria H Ulvmar
  • Kathrin Werth
  • Asolina Braun
  • Poonam Kelay
  • Elin Hub
  • Kathrin Eller
  • Li Chan
  • Beth Lucas
  • Igor Novitzky-Basso
  • Kyoko Nakamura
  • Thomas Rülicke
  • Robert J B Nibbs
  • Tim Worbs
  • Reinhold Förster
  • Antal Rot

Department/unit(s)

Publication details

JournalNature immunology
DateAccepted/In press - 4 Apr 2014
DatePublished (current) - 11 May 2014
Issue number7
Volume15
Number of pages8
Pages (from-to)623-630
Original languageEnglish

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.

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