CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia

Buonamici, Silvia; Trimarchi, Thomas; Ruocco, Maria Grazia; Reavie, Linsey B.; Cathelin, Séverine; Mar, Brenton G.; Klinakis, Apostolos; Lukyanov, Yevgeniy; Tseng, Jen-Chieh; Şen, Filiz; Gehrie, Eric A.; Li, Mengling; Newcomb, Elizabeth W.; Zavadil, Jiří; Meruelo, Daniel; Lipp, Martin; Ibrahim, Sherif; Efstratiadis, Argiris; Zagzag, David; Bromberg, Jonathan S.; Dustin, Michael L.; Aifantis, Iannis

doi:10.1038/nature08020

Cited by 241 publications

(259 citation statements)

References 28 publications

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“…1A). The chemokine CCL19 is constitutively expressed on BBB endothelium and was proposed to mediate infiltration of chemokine (C-C motif) receptor 7 (CCR7) + T cells into the CNS [19,20]. Both our WT and PSGL-1 −/− T-cell lines did not bind a CCL19 Ig fusion protein, confirming that our T cells were CCR7 neg effector/memory T cells [21].…”

Section: Establishment Of Effector Memory Wt and Psgl-1 −/− Sjl/j T-csupporting

confidence: 51%

PSGL‐1 and E/P‐selectins are essential for T‐cell rolling in inflamed CNS microvessels but dispensable for initiation of EAE

et al. 2014

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T-cell migration across the blood-brain barrier is a crucial step in the pathogenesis of EAE, an animal model for MS. Live cell imaging studies demonstrated that P-selectin glycoprotein ligand-1 (PSGL-1) and its endothelial ligands E-and P-selectin mediate the initial rolling of T cells in brain vessels during EAE. As functional absence of PSGL-1 or E/P-selectins does not result in ameliorated EAE, we speculated that T-cell entry into the spinal cord is independent of PSGL-1 and E/P-selectin. Performing intravital microscopy, we observed the interaction of WT or PSGL-1 −/− proteolipid protein-specific T cells in inflamed spinal cord microvessels of WT or E/P-selectin −/− SJL/J mice during EAE. T-cell rolling but not T-cell capture was completely abrogated in the absence of either PSGL-1 or E-and P-selectin, resulting in a significantly reduced number of T cells able to firmly adhere in the inflamed spinal cord microvessels, but did not lead to reduced T-cell invasion into the CNS parenchyma. Thus, PSGL-1 interaction with E/P-selectin is essential for T-cell rolling in inflamed spinal cord microvessels during EAE. Taken together with previous observations, our findings show that T-cell rolling is not required for successful T-cell entry into the CNS and initiation of EAE.Keywords: Blood-brain barrier r Experimental autoimmune encephalomyelitis r P-selectin r P-selectin glycoprotein ligand-1 r T-cell rolling Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionIn MS, and in its animal model, EAE, neuro-Ag-specific CD4 + (where CD is cluster of differentiation) T cells breach the bloodbrain barrier (BBB) and gain access to the CNS, where they cause inflammation, demyelination, and BBB breakdown leading to the clinical manifestation of these diseases. T-cell migration across the BBB is a multi-step process mediated by the sequential interaction of different adhesion and/or signaling molecules on the T cells and Correspondence: Prof. Britta Engelhardt e-mail: bengel@tki.unibe.ch the highly specialized endothelium of the BBB [1]. The discovery that α4β1-integrin plays a critical role in T-cell trafficking across the BBB during EAE has led to the development of a humanized monoclonal anti-α4-integrin Ab (natalizumab) for the treatment of MS [2].In vivo live cell imaging studies have provided direct evidence that the multistep extravasation of encephalitogenic T cells across the spinal cord microvasculature during initiation of EAE is unique [3]. Initiation of T-cell interaction with the spinal cord microvascular endothelium takes place in the absence of rolling and is rather mediated by α4-integrin-mediated G-protein-independent capture and subsequent G-protein-dependent arrest of the T cells in spinal cord microvessels [3]. Once neuroinflammation iswww.eji-journal.eu 2288 Karthik Sathiyanadan et al. Eur. J. Immunol. 2014. 44: 2287-2294 ongoing, it is mostly T-cell rolling with a few alternative capture events also detected, which characterize th...

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Section: Establishment Of Effector Memory Wt and Psgl-1 −/− Sjl/j T-csupporting

confidence: 51%

PSGL‐1 and E/P‐selectins are essential for T‐cell rolling in inflamed CNS microvessels but dispensable for initiation of EAE

et al. 2014

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“…Mast cells have long been known to drive angiogenesis by sustaining new vessel formation and tumor growth [13]. Other examples are mutation of p53 in tumor cells, able to trans-activate CXCL1 [14] and of Notch1 in T cell-acute lymphocytic leukemia, up-regulating CCR7 expression [15].…”

Section: Chemokines As Targets Of Genetic Lesions Causing Cancermentioning

confidence: 99%

“…breast, melanoma, gastric, non-small cell lung cancer, head and neck tumors, colorectal carcinoma), CCR7 is upregulated and mediates tumor cell dissemination to lymph nodes [101][102][103][104][105][106]. In a recent study, brain infiltration by T-cell leukemic blasts was mediated by CCR7 [15]. Members of the CCR family are also used by tumor cells to spread to specific tissues such as the skin, the gut and the liver.…”

Section: Tumor Cell Invasion and Migration To Distant Organsmentioning

confidence: 99%

Chemokines in cancer related inflammation

Allavena

Germano

Marchesi

et al. 2011

Experimental Cell Research

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Chemokines are key players of the cancer-related inflammation. Chemokine ligands and receptors are downstream of genetic events that cause neoplastic transformation and are abundantly expressed in chronic inflammatory conditions which predispose to cancer. Components of the chemokine system affect multiple pathways of tumor progression including: leukocyte recruitment, neo-angiogenesis, tumor cell proliferation and survival, invasion and metastasis.Evidence in pre-clinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies

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“…CCR7, CCR9, CXCR1, and CXCR2 are also detected in tumor cells and their ligands can induce the chemotaxis of the corresponding receptor-expressing cells [37][38][39][40]. These chemokines can serve as inducers of invasion within the primary tumor and dissemination to distant organs (Figure 1).…”

Section: Direct Effects On Cancer Cellsmentioning

confidence: 99%