Semaphorin 7A Promotes Chemokine-Driven Dendritic Cell Migration

Anoek van Rijn, Leonie Paulis, Joost te Riet, Angela Vasaturo, Inge Reinieren-Beeren, Alie van der Schaaf, Arthur J. Kuipers, Luuk P. Schulte, Bart C. Jongbloets, R. Jeroen Pasterkamp, Carl G. Figdor*, Annemiek B. van Spriel, Sonja I. Buschow

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Dendritic cell (DC) migration is essential for efficient host defense against pathogens and cancer, as well as for the efficacy of DC-based immunotherapies. However, the molecules that induce the migratory phenotype of DCs are poorly defined. Based on a largescale proteome analysis of maturing DCs, we identified the GPI-anchored protein semaphorin 7A (Sema7A) as being highly expressed on activated primary myeloid and plasmacytoid DCs in human and mouse. We demonstrate that Sema7A deficiency results in impaired chemokine CCL21-driven DC migration in vivo. Impaired formation of actin-based protrusions, resulting in slower three-dimensional migration, was identified as the mechanism underlying the DC migration defect. Furthermore, we show, by atomic force microscopy, that Sema7A decreases adhesion strength to extracellular matrix while increasing the connectivity of adhesion receptors to the actin cytoskeleton. This study demonstrates that Sema7A controls the assembly of actin-based protrusions that drive DC migration in response to CCL21.

Original languageEnglish
Pages (from-to)459-468
Number of pages10
JournalJournal of Immunology
Volume196
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

Keywords

  • PLEXIN C1
  • LEUKOCYTE MIGRATION
  • RECEPTOR CCR7
  • INTEGRIN
  • ADHESION
  • MECHANISMS
  • GENERATION
  • GRADIENTS
  • RESPONSES
  • COFILIN

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