TY - JOUR
T1 - CCL20 is a novel ligand for the scavenging atypical chemokine receptor 4
AU - Matti, Christoph
AU - D'Uonnolo, Giulia
AU - Artinger, Marc
AU - Melgrati, Serena
AU - Salnikov, Angela
AU - Thelen, Sylvia
AU - Purvanov, Vladimir
AU - Strobel, Tobias D.
AU - Spannagel, Lisa
AU - Thelen, Marcus
AU - Legler, Daniel F.
N1 - Publisher Copyright:
© 2019 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals, Inc. on behalf of Society for Leukocyte Biology
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - ACKR4
KW - CCL19
KW - CCL20
KW - CCL21
KW - CCL25
KW - atypical chemokine receptor
KW - chemokine scavenging
KW - β-arrestin
UR - http://www.scopus.com/inward/record.url?scp=85085898412&partnerID=8YFLogxK
U2 - 10.1002/JLB.2MA0420-295RRR
DO - 10.1002/JLB.2MA0420-295RRR
M3 - Article
C2 - 32533638
AN - SCOPUS:85085898412
SN - 0741-5400
VL - 107
SP - 1137
EP - 1154
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 6
ER -