Systematic reassessment of chemokine-receptor pairings confirms CCL20 but not CXCL13 and extends the spectrum of ACKR4 agonists to CCL22

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Max Meyrath¹  Nathan Reynders¹  Tomasz Uchański¹  Andy Chevigné¹  Martyna Szpakowska¹ 

[1] Immuno-Pharmacology and Interactomics, Department of Infection and Immunity, Luxembourg Institute of Health;Faculty of Science, Technology and Communication, University of Luxembourg

关键词: ACKR2;    ACKR3;    ACKR4;    CCL20;    CCL22;    CCR4;    CCR6;    CCR7;    CCX-CKR;   

DOI  :  10.1002/JLB.2AB0520-275R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Atypical chemokine receptors (ACKRs) have emerged as important regulators or scavengers of homeostatic and inflammatory chemokines. Among these atypical receptors, ACKR4 is reported to bind the homeostatic chemokines CCL19, CCL21, CCL25 and CXCL13. In a recent study by Matti et al., the authors show that ACKR4 is also a receptor for CCL20, previously established to bind to CCR6 only. They provide convincing evidence that, just as for its other chemokine ligands, ACKR4 rapidly internalizes CCL20 both in vitro and in vivo. Independently of this discovery, we undertook a screening program aiming at reassessing the activity of the 43 human chemokines toward ACKR4 using a highly sensitive β-arrestin recruitment assay. This systematic analysis confirmed CCL20 as a new agonist ligand for ACKR4 in addition to CCL19, CCL21, and CCL25. Furthermore, CCL22, which plays an important role in both homeostasis and inflammatory responses, and is known as a ligand for CCR4 and ACKR2 was found to also act as a potent partial agonist of ACKR4. In contrast, agonist activity of CXCL13 toward ACKR4 was disproved. This independent wide-range systematic study confirms the pairing of CCL20 with ACKR4 newly discovered by Matti and co-authors, and further refines the spectrum of chemokines activating ACKR4.

【 授权许可】

CC BY