Changes in the motility, morphology, and F-actin architecture of human dendritic cells in an in vitro model of dendritic cell development

Shutt, Damon C.; Daniels, Karla J.; Carolan, Edward J.; Hill, Aaron C.; Soll, David R.

doi:10.1002/1097-0169(200007)46:3<200::aid-cm5>3.0.co;2-m

Cited by 43 publications

(21 citation statements)

References 60 publications

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“…While migrating toward the T cell zones of the draining lymph nodes (LNs), DCs remodel their chemokine receptor profile, by upregulating CCR7, guiding them toward its ligands CCL19 and CCL21, which are secreted by stromal cells in the T cell zone (7). This differentiation process is accompanied by a dramatic reorganization of the actin cytoskeleton (8), which is mediated via the family of Rho GTPases, including Rho, Rac, and Cdc42, and enables the rapid migration of DCs to draining lymphoid organs.…”

Section: Endritic Cells (Dcs) Play a Central Role In The Initiationmentioning

confidence: 99%

Four-and-a-Half LIM Domain Protein 2 Is a Novel Regulator of Sphingosine 1-Phosphate Receptor 1 in CCL19-Induced Dendritic Cell Migration

König¹,

Diehl

Rommerscheidt-Fuss³

et al. 2010

The Journal of Immunology

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Section: Endritic Cells (Dcs) Play a Central Role In The Initiationmentioning

confidence: 99%

Four-and-a-Half LIM Domain Protein 2 Is a Novel Regulator of Sphingosine 1-Phosphate Receptor 1 in CCL19-Induced Dendritic Cell Migration

König¹,

Diehl

Rommerscheidt-Fuss³

et al. 2010

The Journal of Immunology

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“…In addition to their phenotypic and functional features, DCs show a specific morphology that distinguishes them from others of the immune system, i.e., the dendritic-like protrusions. Accordingly, DCs need a dynamic organization of cytoskeleton, which can render them capable of a flexible activity leading to their phenotypic and migratory properties [4,5]. The actin microfilament integrity and function are pre-requisites for the occurrence of important events associated to cell polarization and movements as well as to activities such as antigen presentation or phagocytosis [6].…”

Section: Introductionmentioning

confidence: 99%

Differentiation of monocyte‐derived dendritic cells is associated with upregulation and activation of Rac‐1 small GTPase

Giammarioli¹,

Gambardella²,

Quaranta³

et al. 2006

FEBS Letters

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Critical changes occurring in Rac-1 molecule, a cytoskeleton organizing small GTPase associated with cell ruffling, have been analyzed in dendritic cells (DCs) derived from monocytes cultured with granulocyte-macrophage colony-stimulating factor and IFN-a or IL-4. Although with different kinetics, both agents induced activation of Rac-1 molecule and, more importantly, an upregulation of both protein expression and mRNA transcription. These findings strengthen the role of Rac-1 molecule in the induction of DC differentiation and suggest that, besides its activation, the upregulation of Rac-1 molecule might also play a role in the acquisition of DC mature phenotype.

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“…Unlike CXCR4 and CCR7, no significant loss of expression of GAPDH could be demonstrated (Fig. 3, row 4), an effect that was confirmed by Affymetrix gene-chip analysis.It has been demonstrated that the ability of cells (especially DCs) to migrate also depends on the correct function of the cytoskeleton (Shutt et al, 2000;Wehrle-Haller & Imhof, 2003). To determine whether the observed loss of ability to migrate was due to significant changes in the expression of cytoskeleton components, we also analysed the expression profile of b-actin, a molecule highly relevant for the cytoskeleton (Fig.…”

mentioning

confidence: 99%

Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration

Prechtel

Turza

Kobelt

et al. 2005

Journal of General Virology

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Herpes simplex virus type 1 (HSV-1) is able to establish latency in infected individuals. In order to characterize potential new immune-escape mechanisms, mature dendritic cells (DCs) were infected with HSV-1 and total cellular RNA was isolated from infected and mock-infected populations at different time points. RNA profiling on Affymetrix Human Genome U133A arrays demonstrated a dramatic downregulation of the migration-mediating surface molecules CCR7 and CXCR4, an observation that was further confirmed by RT-PCR and fluorescence-activated cell sorting analyses. Furthermore, migration assays revealed that, upon infection of mature DCs, CCR7-and CXCR4-mediated migration towards the corresponding CCL19 and CXCL12 chemokine gradients was strongly reduced. It is noteworthy that the infection of immature DCs with HSV-1 prior to maturation led to a failure of CCR7 and CXCR4 upregulation during DC maturation and, as a consequence, also induced a block in their migratory capacity. Additional migration assays with a Dvhs mutant virus lacking the virion host shutoff (vhs) gene, which is known to degrade cellular mRNAs, suggested a vhs-independent mechanism. These results indicate that HSV-1-infected mature DCs are limited in their capacity to migrate to secondary lymphoid organs, the areas of antigen presentation and T-cell stimulation, thus inhibiting an antiviral immune response. This represents a novel, previously unrecognized mechanism for HSV-1 to escape the human immune system. INTRODUCTIONDendritic cells (DCs) are bone marrow-derived leukocytes and represent the best-known group of antigen-presenting cells (APCs) today. In order to induce specific T cellmediated immune responses, they act as the sentinels of the immune system and lie in wait in an immature state in almost all peripheral tissues (Banchereau & Steinman, 1998). Maturation is induced by contact of immature DCs with various products of infectious agents (Aliprantis et al., 1999;Brightbill et al., 1999;Cella et al., 1999). During maturation, DCs lose their ability to take up antigens and migrate from the sites of antigen accumulation to the areas of antigen presentation, primarily the T-cell zones of the secondary lymphoid organs (Banchereau & Steinman, 1998;Ridge et al., 1998).Immature DCs differ significantly from mature DCs in their response to specific chemokines, their ability to migrate and their capacity to stimulate immune responses (Gunn, 2003). Whilst immature DCs respond to many CC and CXC chemokines, such as CCL3 (MIP-1a), CCL4 (MIP-1b), CCL5 (RANTES) and CCL20 (MIP-3a), the expression or activity of the corresponding receptors is reduced or abolished completely in mature DCs 1998). As a consequence of the enhanced expression of CCR7 and CXCR4, mature DCs show an increased response to CCL19 (MIP-3b) and CXCL12 (SDF-1a) (Cavanagh & Von Andrian, 2002; Delgado et al., 1998; Förster et al., 1999;Gunn et al., 1999). The necessity of CCR7 expression for the induction of a primary immune response (Förster et al., 1999;Parlato et al., 2001) has ...

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Changes in the motility, morphology, and F-actin architecture of human dendritic cells in an in vitro model of dendritic cell development

Cited by 43 publications

References 60 publications

Four-and-a-Half LIM Domain Protein 2 Is a Novel Regulator of Sphingosine 1-Phosphate Receptor 1 in CCL19-Induced Dendritic Cell Migration

Four-and-a-Half LIM Domain Protein 2 Is a Novel Regulator of Sphingosine 1-Phosphate Receptor 1 in CCL19-Induced Dendritic Cell Migration

Differentiation of monocyte‐derived dendritic cells is associated with upregulation and activation of Rac‐1 small GTPase

Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration

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