التفاصيل البيبلوغرافية
| العنوان: |
Netrin-1 Augments Chemokinesis in CD4+ T Cells In Vitro and Elicits a Proinflammatory Response In Vivo. |
| المؤلفون: |
Boneschansker, Leo1,2,3, Hironao Nakayama4, Eisenga, Michele1, Wedel, Johannes1,2, Klagsbrun, Michael4, Irimia, Daniel3, Briscoe, David M.1,2 david.briscoe@childrens.harvard.edu |
| المصدر: |
Journal of Immunology. 8/15/2016, Vol. 197 Issue 4, p1389-1398. 10p. |
| مصطلحات موضوعية: |
*NETRINS, *CHEMOKINES, *CELL adhesion, *T cells, *IN vivo studies, *CELL migration, *CYTOSKELETON |
| مستخلص: |
Netrin-1 is a neuronal guidance cue that regulates cellular activation, migration, and cytoskeleton rearrangement in multiple cell types. It is a chemotropic protein that is expressed within tissues and elicits both attractive and repulsive migratory responses. Netrin-1 has recently been found to modulate the immune response via the inhibition of neutrophil and macrophage migration. However, the ability of Netrin-1 to interact with lymphocytes and its in-depth effects on leukocyte migration are poorly understood. In this study, we profiled the mRNA and protein expression of known Netrin-1 receptors on human CD4+ T cells. Neogenin, uncoordinated-5 (UNC5)A, and UNC5B were expressed at low levels in unstimulated cells, but they increased following mitogendependent activation. By immunofluorescence, we observed a cytoplasmic staining pattern of neogenin and UNC5A/B that also increased following activation. Using a novel microfluidic assay, we found that Netrin-1 stimulated bidirectional migration and enhanced the size of migratory subpopulations of mitogen-activated CD4+ T cells, but it had no demonstrable effects on the migration of purified CD4+CD25+CD127dim T regulatory cells. Furthermore, using a short hairpin RNA knockdown approach, we observed that the promigratory effects of Netrin-1 on T effectors is dependent on its interactions with neogenin. In the humanized SCID mouse, local injection of Netrin-1 into skin enhanced inflammation and the number of neogenin-expressing CD3+ T cell infiltrates. Neogenin was also observed on CD3+ T cell infiltrates within human cardiac allograft biopsies with evidence of rejection. Collectively, our findings demonstrate that Netrin-1/neogenin interactions augment CD4+ T cell chemokinesis and promote cellular infiltration in association with acute inflammation in vivo. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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