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Publication : Dendritic cells distinguish individual chemokine signals through CCR7 and CXCR4.

First Author  Ricart BG Year  2011
Journal  J Immunol Volume  186
Issue  1 Pages  53-61
PubMed ID  21106854 Mgi Jnum  J:168737
Mgi Id  MGI:4936817 Doi  10.4049/jimmunol.1002358
Citation  Ricart BG, et al. (2011) Dendritic cells distinguish individual chemokine signals through CCR7 and CXCR4. J Immunol 186(1):53-61
abstractText  Dendritic cells (DCs) respond to chemotactic signals to migrate from sites of infection to secondary lymphoid organs where they initiate the adaptive immune response. The key chemokines directing their migration are CCL19, CCL21, and CXCL12, but how signals from these chemokines are integrated by migrating cells is poorly understood. Using a microfluidic device, we presented single and competing chemokine gradients to murine bone-marrow derived DCs in a controlled, time-invariant microenvironment. Experiments performed with counter-gradients revealed that CCL19 is 10-100-fold more potent than CCL21 or CXCL12. Interestingly, when the chemoattractive potencies of opposing gradients are matched, cells home to a central region in which the signals from multiple chemokines are balanced; in this region, cells are motile but display no net displacement. Actin and myosin inhibitors affected the speed of crawling but not directed motion, whereas pertussis toxin inhibited directed motion but not speed. These results provide fundamental insight into the processes that DCs use to migrate toward and position themselves within secondary lymphoid organs.
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