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 - Funding Information:
We thank Nicola Catone, Oliver Gerken and Ilona Kindinger for technical assistance with chemokine preparation and Joshua Farber for kindly providing the hCCR9 plasmid. This work is supported by the Swiss National Science Foundation [Sinergia CRSII3_160719 (M.T. and D.F.L.)], the Helmut Horten Foundation (M.T.), the Konstanz Research School Chemical Biology (KoRS‐CB), the Crescere Stiftung Thurgau, the Thurgauische Stiftung für Wissenschaft und Forschung, and the State Secretariat for Education, Research and Innovation (D.F.L.).
Funding Information:
We thank Nicola Catone, Oliver Gerken and Ilona Kindinger for technical assistance with chemokine preparation and Joshua Farber for kindly providing the hCCR9 plasmid. This work is supported by the Swiss National Science Foundation [Sinergia CRSII3_160719 (M.T. and D.F.L.)], the Helmut Horten Foundation (M.T.), the Konstanz Research School Chemical Biology (KoRS-CB), the Crescere Stiftung Thurgau, the Thurgauische Stiftung f?r Wissenschaft und Forschung, and the State Secretariat for Education, Research and Innovation (D.F.L.).
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 - atypical chemokine receptor
KW - CCL19
KW - CCL20
KW - CCL21
KW - CCL25
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 -