CCL19 with CCL21-tail displays enhanced glycosaminoglycan binding with retained chemotactic potency in dendritic cells

Journal of Leukocyte Biology
Astrid Sissel JørgensenGertrud Malene Hjortø

Abstract

CCL19 is more potent than CCL21 in inducing chemotaxis of human dendritic cells (DC). This difference is attributed to 1) a stronger interaction of the basic C-terminal tail of CCL21 with acidic glycosaminoglycans (GAGs) in the environment and 2) an autoinhibitory function of this C-terminal tail. Moreover, different receptor docking modes and tissue expression patterns of CCL19 and CCL21 contribute to fine-tuned control of CCR7 signaling. Here, we investigate the effect of the tail of CCL21 on chemokine binding to GAGs and on CCR7 activation. We show that transfer of CCL21-tail to CCL19 (CCL19CCL21-tail ) markedly increases binding of CCL19 to human dendritic cell surfaces, without impairing CCL19-induced intracellular calcium release or DC chemotaxis, although it causes reduced CCR7 internalization. The more potent chemotaxis induced by CCL19 and CCL19CCL21-tail compared to CCL21 is not transferred to CCL21 by replacing its N-terminus with that of CCL19 (CCL21CCL19-N-term ). Measurements of cAMP production in CHO cells uncover that CCL21-tail transfer (CCL19CCL21-tail ) negatively affects CCL19 potency, whereas removal of CCL21-tail (CCL21tailless ) increases signaling compared to full-length CCL21, indicating that the tail n...Continue Reading

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Citations

Apr 13, 2019·Immunological Reviews·Tim Lämmermann, Wolfgang Kastenmüller
May 21, 2020·Frontiers in Cellular Neuroscience·Natalia PetersenMette Marie Rosenkilde
Jan 2, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Anwar SalemKamyar Afarinkia
Aug 8, 2021·International Journal of Molecular Sciences·Emma Probst BrandumGertrud Malene Hjortø
Mar 18, 2020·Biochemistry·Natasha A MoussourasMichael B Dwinell
Oct 5, 2021·Frontiers in Immunology·Edith Uetz-von AllmenDaniel F Legler

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