Polysialylation controls dendritic cell trafficking by regulating chemokine recognition

Eva Kiermaier, Christine Moussion, Christopher T. Veldkamp, Rita Gerardy-Schahn, Ingrid De Vries, Larry G. Williams, Gary R. Chaffee, Andrew J. Phillips, Friedrich Freiberger, Richard Imre, Deni Taleski, Richard J. Payne, Asolina Braun, Reinhold Förster, Karl Mechtler, Martina Mühlenhoff, Brian F. Volkman, Michael Sixt

Research output: Contribution to journalArticleResearchpeer-review

73 Citations (Scopus)

Abstract

The addition of polysialic acid to N- and/or O-linked glycans, referred to as polysialylation, is a rare posttranslational modification that is mainly known to control the developmental plasticity of the nervous system. Here we show that CCR7, the central chemokine receptor controlling immune cell trafficking to secondary lymphatic organs, carries polysialic acid. This modification is essential for the recognition of the CCR7 ligand CCL21. As a consequence, dendritic cell trafficking is abrogated in polysialyltransferase-deficient mice, manifesting as disturbed lymph node homeostasis and unresponsiveness to inflammatory stimuli. Structure-function analysis of chemokine-receptor interactions reveals that CCL21 adopts an autoinhibited conformation, which is released upon interaction with polysialic acid. Thus, we describe a glycosylation-mediated immune cell trafficking disorder and its mechanistic basis.

Original languageEnglish
Pages (from-to)186-190
Number of pages5
JournalScience
Volume351
Issue number6269
DOIs
Publication statusPublished - 8 Jan 2016
Externally publishedYes

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