CCL20 is a novel ligand for the scavenging atypical chemokine receptor 4

Christoph Matti, Giulia D'Uonnolo, Marc Artinger, Serena Melgrati, Angela Salnikov, Sylvia Thelen, Vladimir Purvanov, Tobias D. Strobel, Lisa Spannagel, Marcus Thelen*, Daniel F. Legler*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)


The chemokine CCL20 is broadly produced by endothelial cells in the liver, the lung, in lymph nodes and mucosal lymphoid tissues, and recruits CCR6 expressing leukocytes, particularly dendritic cells, mature B cells, and subpopulations of T cells. How CCL20 is systemically scavenged is currently unknown. Here, we identify that fluorescently labeled human and mouse CCL20 are efficiently taken-up by the atypical chemokine receptor ACKR4. CCL20 shares ACKR4 with the homeostatic chemokines CCL19, CCL21, and CCL25, although with a lower affinity. We demonstrate that all 4 human chemokines recruit β-arrestin1 and β-arrestin2 to human ACKR4. Similarly, mouse CCL19, CCL21, and CCL25 equally activate the human receptor. Interestingly, at the same chemokine concentration, mouse CCL20 did not recruit β-arrestins to human ACKR4. Further cross-species analysis suggests that human ACKR4 preferentially takes-up human CCL20, whereas mouse ACKR4 similarly internalizes mouse and human CCL20. Furthermore, we engineered a fluorescently labeled chimeric chemokine consisting of the N-terminus of mouse CCL25 and the body of mouse CCL19, termed CCL25_19, which interacts with and is taken-up by human and mouse ACKR4.

Original languageEnglish
Pages (from-to)1137-1154
Number of pages18
JournalJournal of Leukocyte Biology
Issue number6
Publication statusPublished - 1 Jun 2020
Externally publishedYes


  • ACKR4
  • CCL19
  • CCL20
  • CCL21
  • CCL25
  • atypical chemokine receptor
  • chemokine scavenging
  • β-arrestin


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