biostudies-literatureUnknown118(17)Bastow CRLeukocyte homing driven by the chemokine CCL21 is pivotal for adaptive immunity because it controls dendritic cell (DC) and T cell migration through CCR7. ACKR4 scavenges CCL21 and has been shown to play an essential role in DC trafficking at the steady state and during immune responses to tumors and cutaneous inflammation. However, the mechanism by which ACKR4 regulates peripheral DC migration is unknown, and the extent to which it regulates CCL21 in steady-state skin and lymph nodes (LNs) is contested. Specifically, our previous findings that CCL21 levels are increased in LNs of ACKR4-deficient mice [I. Comerford et al., Blood 116, 4130-4140 (2010)] were refuted [M. H. Ulvmar et al., Nat. Immunol. 15, 623-630 (2014)], and no differences in CCL21 levels in steady-state skin of ACKR4-deficProceedings of the National Academy of Sciences of the United States of Americae2025763118https://www.ebi.ac.uk/biostudies/studies/S-EPMC8092586biostudies-literatureScavenging of soluble and immobilized CCL21 by ACKR4 regulates peripheral dendritic cell emigration.PMC8092586Comerford ICaon AYoung CMcColl SRFrazer IHBastow CRMcKenzie DRMueller SNKara EEDevi SHarvey NCondina MRTolley LHoffmann PBunting MDfalseScavenging of soluble and immobilized CCL21 by ACKR4 regulates peripheral dendritic cell emigration.Leukocyte homing driven by the chemokine CCL21 is pivotal for adaptive immunity because it controls dendritic cell (DC) and T cell migration through CCR7. ACKR4 scavenges CCL21 and has been shown to play an essential role in DC trafficking at the steady state and during immune responses to tumors and cutaneous inflammation. However, the mechanism by which ACKR4 regulates peripheral DC migration is unknown, and the extent to which it regulates CCL21 in steady-state skin and lymph nodes (LNs) is contested. Specifically, our previous findings that CCL21 levels are increased in LNs of ACKR4-deficient mice [I. Comerford et al., Blood 116, 4130-4140 (2010)] were refuted [M. H. Ulvmar et al., Nat. Immunol. 15, 623-630 (2014)], and no differences in CCL21 levels in steady-state skin of ACKR4-defic2021-01-01T00:00:00Z2021 Apr2025-04-26T23:43:00.855Z2025-04-06T17:39:17.693ZS-EPMC80925863387560110.1073/pnas.2025763118