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Cross-talk between TCR and CCR7 signaling sets a temporal threshold for enhanced T lymphocyte migration

Cross-talk between TCR and CCR7 signaling sets a temporal threshold for enhanced T lymphocyte migration

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SCHÄUBLE, Karin, Mark A. HAUSER, Eva SINGER, Marcus GRÖTTRUP, Daniel LEGLER, 2011. Cross-talk between TCR and CCR7 signaling sets a temporal threshold for enhanced T lymphocyte migration. In: The Journal of Immunology. 187(11), pp. 5645-5652. ISSN 0022-1767. eISSN 1550-6606

@article{Schauble2011-12-01Cross-18133, title={Cross-talk between TCR and CCR7 signaling sets a temporal threshold for enhanced T lymphocyte migration}, year={2011}, doi={10.4049/jimmunol.1101850}, number={11}, volume={187}, issn={0022-1767}, journal={The Journal of Immunology}, pages={5645--5652}, author={Schäuble, Karin and Hauser, Mark A. and Singer, Eva and Gröttrup, Marcus and Legler, Daniel} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/18133"> <dc:contributor>Singer, Eva</dc:contributor> <dcterms:title>Cross-talk between TCR and CCR7 signaling sets a temporal threshold for enhanced T lymphocyte migration</dcterms:title> <dc:creator>Schäuble, Karin</dc:creator> <dc:contributor>Schäuble, Karin</dc:contributor> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103605204-4002607-1"/> <dc:creator>Gröttrup, Marcus</dc:creator> <dc:creator>Singer, Eva</dc:creator> <dcterms:bibliographicCitation>Publ. in: The journal of immunology ; 187 (2011), 11. - S. 5645-5652 .</dcterms:bibliographicCitation> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-02-01T08:22:53Z</dc:date> <dc:contributor>Legler, Daniel</dc:contributor> <dc:contributor>Hauser, Mark A.</dc:contributor> <dc:language>eng</dc:language> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/18133"/> <dc:creator>Hauser, Mark A.</dc:creator> <dc:contributor>Gröttrup, Marcus</dc:contributor> <dcterms:issued>2011-12-01</dcterms:issued> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-02-01T08:22:53Z</dcterms:available> <dcterms:abstract xml:lang="eng">Lymphocyte homing to, and motility within, lymph nodes is regulated by the chemokine receptor CCR7 and its two ligands CCL19 and CCL21. There, lymphocytes are exposed to a number of extracellular stimuli that influence cellular functions and determine the cell fate. In this study, we assessed the effect of TCR engagement on CCR7-mediated cell migration. We found that long-term TCR triggering of freshly isolated human T cells through CD3/CD28 attenuated CCR7-driven chemotaxis, whereas short-term activation significantly enhanced CCR7-mediated, but not CXCR4-mediated, migration efficiency. Short-term activation most prominently enhanced the migratory response of naive T cells of both CD4 and CD8 subsets. We identified distinct roles for Src family kinases in modulating CCR7-mediated T cell migration. We provide evidence that Fyn, together with Ca(2+)-independent protein kinase C isoforms, kept the migratory response of naive T cells toward CCL21 at a low level. In nonactivated T cells, CCR7 triggering induced a Fyn-dependent phosphorylation of the inhibitory Tyr505 of Lck. Inhibiting Fyn in these nonactivated T cells prevented the negative regulation of Lck and facilitated high CCR7-driven T cell chemotaxis. Moreover, we found that the enhanced migration of short-term activated T cells was accompanied by a synergistic, Src-dependent activation of the adaptor molecule linker for activation of T cells. Collectively, we characterize a cross-talk between the TCR and CCR7 and provide mechanistic evidence that the activation status of T cells controls lymphocyte motility and sets a threshold for their migratory response.</dcterms:abstract> <dc:creator>Legler, Daniel</dc:creator> <dc:rights>deposit-license</dc:rights> </rdf:Description> </rdf:RDF>

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