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• W2148371571 endingPage "849" @default.
• W2148371571 startingPage "839" @default.
• W2148371571 abstract "Tissue inflammation induces rapid mobilization of antigen-charged dendritic cells (DCs), which migrate to draining lymph nodes via afferent lymphatics to elicit the immune response. This increase in DC trafficking has been shown to require integrin-dependent adhesion to ICAM-1 and VCAM-1, expressed on inflamed lymphatic endothelium. In addition, both constitutive- and inflammation-induced DC migration involves the chemokine CCL21, which most likely triggers integrin activation on DC via its receptor CCR7. Recently, however, conflicting evidence has suggested that DC entry occurs independently of integrins, implying that the role of CCL21 in lymphatics is purely chemotactic. Hence, while CCL21 is reported to be inducible during inflammation, the details of this induction and the role of CCL21 during initial DC trafficking are unclear. Here, we have characterized both the production of CCL21 and the mechanism of its action in DC transmigration using primary human dermal lymphatic endothelial cells (HDLECs) and a mouse model of skin contact hypersensitivity. We showed that CCL21 is constitutively expressed intracellularly but rapidly secreted after exposure to the inflammatory cytokine tumour necrosis factor (TNF) α following de novo RNA and protein synthesis. Furthermore, using in vitro transmigration assays, we showed that endogenous HDLEC-derived CCL21 stimulates DC translymphatic migration by a predominantly chemotactic mechanism in resting HDLEC and by a β2 integrin-mediated mechanism in TNFα-stimulated HDLEC. These results imply a direct role for CCL21 in lymphatic transmigration that involves the selective use of integrin activation in inflammation." @default.
• W2148371571 created "2016-06-24" @default.
• W2148371571 creator A5030823404 @default.
• W2148371571 creator A5062882861 @default.
• W2148371571 date "2010-08-25" @default.
• W2148371571 modified "2023-10-05" @default.
• W2148371571 title "Inflammation-induced secretion of CCL21 in lymphatic endothelium is a key regulator of integrin-mediated dendritic cell transmigration" @default.
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• W2148371571 doi "https://doi.org/10.1093/intimm/dxq435" @default.
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• W2148371571 hasPublicationYear "2010" @default.
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