Constitutive Plasmacytoid Dendritic Cell Migration to the Splenic White Pulp Is Cooperatively Regulated by CCR7- and CXCR4-Mediated Signaling

Umemoto, Eiji; Otani, Kazuhiro; Ikeno, Takashi; García, Noel Verján; Hayasaka, Haruko; Bai, Zhongbin; Jang, Myoung Ho; Tanaka, Toshiyuki; Nagasawa, Takashi; Ueda, Koji; Miyasaka, Masayuki

doi:10.4049/jimmunol.1200802

Cited by 56 publications

(41 citation statements)

References 46 publications

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“…The chemotactic effects of CXCL12 on T cells is well established, yet whether active CXCL12 is soluble, immobilized or a combination thereof in vivo is unclear. The surface-bound CXCL12 distribution has been examined in vivo by antibody staining [6] or by imaging CXCL12-GFP knock-in mice [41]; however, information about soluble CXCL12 is currently inaccessible. Studies have suggested that the chemokine CCL21 is bound to extracellular matrix or to cell membranes through interactions with glycosaminoglycans (GAGs).…”

Section: Discussionmentioning

confidence: 99%

Linking morphodynamics and directional persistence of T lymphocyte migration

Liu

Welf

Haugh

2015

J. R. Soc. Interface.

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T cells play a central role in the adaptive immune response, and their directed migration is essential for homing to sites of antigen presentation. Like neutrophils, T lymphocytes are rapidly moving cells that exhibit amoeboid movement, characterized by a definitive polarity with F-actin concentrated at the front and myosin II elsewhere. In this study, we used total internal reflection fluorescence (TIRF) microscopy to monitor the cells' areas of contact with a surface presenting adhesive ICAM-1 and the chemokine, CXCL12/ SDF-1. Our analysis reveals that T-cell migration and reorientation are achieved by bifurcation and lateral separation of protrusions along the leading membrane edge, followed by cessation of one of the protrusions, which acts as a pivot for cell turning. We show that the distribution of bifurcation frequencies exhibits characteristics of a random, spontaneous process; yet, the waiting time between bifurcation events depends on whether or not the pivot point remains on the same side of the migration axis. Our analysis further suggests that switching of the dominant protrusion between the two sides of the migration axis is associated with persistent migration, whereas the opposite is true of cell turning. To help explain the bifurcation phenomenon and how distinct migration behaviours might arise, a spatio-temporal, stochastic model describing F-actin dynamics is offered.

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Section: Discussionmentioning

confidence: 99%

Linking morphodynamics and directional persistence of T lymphocyte migration

Liu

Welf

Haugh

2015

J. R. Soc. Interface.

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“…CXCR4 is expressed constitutively in a large array of tissues such as heart, lung, liver, and spleen [9][10][11][12]. Its ligand is stromal cellderived factor-1a (SDF-1a) [8,13].…”

Section: Introductionmentioning

confidence: 99%

Distribution of CXCR4 and γ-catenin expression pattern in breast cancer subtypes and their relationship to axillary nodal involvement

Sivrikoz¹,

Doğanay²,

Sivrikoz³

et al. 2013

pjp

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Chemokine receptor 4 (CXCR4) and γ-catenin are known to play an important role in development of metastasis in breast cancer. However, there is not enough information about these biological markers' distribution in different breast cancer subtypes, or their relationship to lymph node metastases in each subtype. In this study, staining characteristics of CXCR4 and γ-catenin were analyzed in each breast cancer subtype and their relationship to lymph node involvement explored. There was a statistically significant relationship between CXCR4 and certain tumor subtypes (p < 0.05). Basal-like and HER2 enriched tumors showed strong CXCR4 positivity (45.7%). Furthermore, a significant correlation was discovered between CXCR4 positivity and lymph node involvement (p < 0.05). Among tumor subtypes staining positively with CXCR4, 80% of basal-like, 90% of HER2 enriched, and 78.5% of luminal A showed axillary lymph node involvement. In general, there was a positive relationship between histological grade and CXCR4 expression (p = 0.004). A statistically significant correlation existed between HER2 positivity and γ-catenin expression (p < 0.05). Basal-like and HER2 enriched breast cancer subtypes express CXCR4 staining more often than the other subtypes. Additionally, there is also a positive relationship between lymph node involvement and CXCR4 staining of these subtypes.

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“…CCR7, which determines the accumulation of Ag-loaded mature DCs in T cell-rich areas, is upregulated (25,(33)(34)(35)(36). A recent study also suggested that CXCR4-and CCR7-mediated signaling might cooperatively regulate the migration of DCs into the splenic white pulp (37). Inhibiting the migration of DCs has been used to treat immune diseases.…”

Section: Discussionmentioning

confidence: 99%

Aurintricarboxylic Acid Ameliorates Experimental Autoimmune Encephalomyelitis by Blocking Chemokine-Mediated Pathogenic Cell Migration and Infiltration

Zhang

Wei

Chai

et al. 2013

The Journal of Immunology

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Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by the immune-mediated demyelination and neurodegeneration of the CNS. Overactivation of CD4+ T cells, especially the Th1 and Th17 subpopulations, is thought to be the direct cause of this disease. Aurintricarboxylic acid (ATA), an inhibitor of protein–nucleic acid interaction, has been reported to block with the JAK/STAT signaling pathway that is critical for Th cell differentiation. In this study, we discovered that ATA treatment significantly reduces the clinical score of EAE, but it does not directly inhibit the differentiation of Th1 and Th17 cells in vitro. ATA was found to block the chemotaxis and accumulation of dendritic cells in the spleen of EAE mice before the onset of the disease and to reduce the percentage of Th1 and Th17 cells in the spleen. Further study revealed that ATA also blocks the infiltration of pathogenic T cells into the CNS and blocks the onset of passive EAE. ATA was found to inhibit the functions of many chemokine receptors. By blocking chemokine-mediated migration of dendritic cells and pathogenic T cells, ATA alleviates the pathogenesis of EAE and might be used to treat autoimmune diseases, including multiple sclerosis.

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Constitutive Plasmacytoid Dendritic Cell Migration to the Splenic White Pulp Is Cooperatively Regulated by CCR7- and CXCR4-Mediated Signaling

Cited by 56 publications

References 46 publications

Linking morphodynamics and directional persistence of T lymphocyte migration

Linking morphodynamics and directional persistence of T lymphocyte migration

Distribution of CXCR4 and γ-catenin expression pattern in breast cancer subtypes and their relationship to axillary nodal involvement

Aurintricarboxylic Acid Ameliorates Experimental Autoimmune Encephalomyelitis by Blocking Chemokine-Mediated Pathogenic Cell Migration and Infiltration

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