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Nat Cell Biol. 2016 Jan;18(1):43-53. doi: 10.1038/ncb3284. Epub 2015 Dec 7.

Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells.

Author information

1
Inserm U932, Institut Curie, 12 rue Lhomond, 75005 Paris, France.
2
CNRS UMR144, Institut Curie, 12 rue Lhomond, 75005 Paris, France.
3
Institute for Immunology, Ludwig-Maximilian University of Munich, 80336 Munich, Germany.
4
Van Andel Research Institute, 333 Bostwick Avenue N.E., Grand Rapids, Michigan 49503, USA.
5
Johns Hopkins University School of Medicine, 855 N. Wolfe Street, Baltimore, Maryland 21205, USA.
6
CNRS UMR 7600, Université Pierre et Marie Curie, 4 Place Jussieu, 75005 Paris, France.
7
CNRS FRE 3231, Université Pierre et Marie Curie, 4 Place Jussieu, 75005 Paris, France.

Abstract

Dendritic cell (DC) migration in peripheral tissues serves two main functions: antigen sampling by immature DCs, and chemokine-guided migration towards lymphatic vessels (LVs) on maturation. These migratory events determine the efficiency of the adaptive immune response. Their regulation by the core cell locomotion machinery has not been determined. Here, we show that the migration of immature DCs depends on two main actin pools: a RhoA-mDia1-dependent actin pool located at their rear, which facilitates forward locomotion; and a Cdc42-Arp2/3-dependent actin pool present at their front, which limits migration but promotes antigen capture. Following TLR4-MyD88-induced maturation, Arp2/3-dependent actin enrichment at the cell front is markedly reduced. Consequently, mature DCs switch to a faster and more persistent mDia1-dependent locomotion mode that facilitates chemotactic migration to LVs and lymph nodes. Thus, the differential use of actin-nucleating machineries optimizes the migration of immature and mature DCs according to their specific function.

PMID:
26641718
PMCID:
PMC5885286
DOI:
10.1038/ncb3284
[Indexed for MEDLINE]
Free PMC Article

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