title: Polysialic acid is required for neuropilin-2a/b-mediated control of CCL21-driven chemotaxis of mature dendritic cells and for their migration in vivo.
abstract: Migration of mature dendritic cells (mDCs) to secondary lymphoid organs is required for the development of immunity. Recently, we reported that polysialic acid (PSA) and the transmembrane glycoprotein neuropilin-2 (NRP2) control mDC chemotaxis to CCL21 and that this process is dependent on the C-terminal basic region of the chemokine. Herein, we provide further insight into the molecular components controlling PSA regulated chemotaxis in mDCs. In the present study, we demonstrate that human mDCs express the NRP2 isoforms NRP2a and NRP2b, that both of them are susceptible to polysialylation and that polysialylation is required to specifically enhance chemotaxis toward CCL21 in mDCs. The results presented suggest that PSA attached to NRP2 isoforms acts as a binding module for the CCL21 chemokine, thereby facilitating its presentation to the chemokine receptor CCR7. To investigate the relevance of polysialylation on mDC migration, a xenograft mouse model was used and the migration of human DCs to mouse lymph nodes analyzed. Here, we demonstrate that the depletion of PSA from mDCs results in a drastic reduction in the migration of the cells to draining popliteal lymph nodes. With this finding, we provide first evidence that PSA is a crucial factor for in vivo migration of mDCs to lymph nodes.
authors.affiliation: Departamento de Microbiología Molecular y Biología de las Infecciones, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Rey-Gallardo
authors.forename: Cristina
authors.initials: C
authors.lastname: Delgado-Martín
authors.forename: Rita
authors.initials: R
authors.lastname: Gerardy-Schahn
authors.forename: José L
authors.initials: JL
authors.lastname: Rodríguez-Fernández
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Vega
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000494:pharmacology; D054421:Chemokine CCL21 / Q000494:pharmacology / Q000502:physiology*; D002633:Chemotaxis; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D051379:Mice; D039943:Neuropilin-2 / Q000737:chemistry / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012794:Sialic Acids / Q000378:metabolism*
chemical_list: D054415:Chemokine CCL19; D054421:Chemokine CCL21; D039943:Neuropilin-2; D020033:Protein Isoforms; D012794:Sialic Acids; C021319:polysialic acid