Semaphorin 7A Promotes Chemokine-Driven Dendritic Cell Migration

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 large-scale proteome analysis of maturing DCs,...

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Veröffentlicht in:The Journal of immunology (1950) 2016-01, Vol.196 (1), p.459-468
Hauptverfasser: van Rijn, Anoek, Paulis, Leonie, te Riet, Joost, Vasaturo, Angela, Reinieren-Beeren, Inge, van der Schaaf, Alie, Kuipers, Arthur J, Schulte, Luuk P, Jongbloets, Bart C, Pasterkamp, R Jeroen, Figdor, Carl G, van Spriel, Annemiek B, Buschow, Sonja I
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container_issue 1
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container_title The Journal of immunology (1950)
container_volume 196
creator van Rijn, Anoek
Paulis, Leonie
te Riet, Joost
Vasaturo, Angela
Reinieren-Beeren, Inge
van der Schaaf, Alie
Kuipers, Arthur J
Schulte, Luuk P
Jongbloets, Bart C
Pasterkamp, R Jeroen
Figdor, Carl G
van Spriel, Annemiek B
Buschow, Sonja I
description 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 large-scale 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.
doi_str_mv 10.4049/jimmunol.1403096
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subjects Actin Cytoskeleton - metabolism
Animals
Antigens, CD - genetics
Antigens, CD - physiology
Cell Adhesion
Cell Movement - genetics
Cell Movement - physiology
Cells, Cultured
Chemokine CCL21 - metabolism
Dendritic Cells - physiology
Extracellular Matrix - metabolism
GPI-Linked Proteins - genetics
GPI-Linked Proteins - physiology
Humans
Mice
Mice, Knockout
Microscopy, Atomic Force
RNA Interference
RNA, Small Interfering
Semaphorins - genetics
Semaphorins - physiology
title Semaphorin 7A Promotes Chemokine-Driven Dendritic Cell Migration
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