Leukocytes use the chemokine receptor CCR7 to traffic from interstitial tissues into lymphatics and draining lymph nodes, in response to the chemokines CCL19 and CCL21. In Science, Kiermaier et al. reveal that polysialylation of CCR7 regulates dendritic cell (DC) trafficking. Mice lacking the polysialyltransferase ST8Sia IV fail to post-translationally modify CCR7 and have diminished lymph node cellularity. ST8Sia IV–deficient DCs fail to migrate in response to CCL21; however, their migration to CCL19 remains unaltered. Accordingly, CCL21 exists in an auto-inhibited conformation. This autoinhibition is relieved by interaction with polysialyl carbohydrate chains of CCR7, which allows ST8Sia IV–sufficient DCs to respond to CCL21. Further investigation is warranted to understand why such regulatory mechanisms arose to 'fine-tune' DC migration and how this modification is altered during infection or other disease states.
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Dempsey, L. CCR7 polysialylation. Nat Immunol 17, 121 (2016). https://doi.org/10.1038/ni.3381
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DOI: https://doi.org/10.1038/ni.3381
