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Dendritic cells (DCs) creep like amoebas into lymph vessels. Pflicke and Sixt catch them squeezing through minute pores and trap doors to enter.
Two barriers surround vessels—the endothelium and the basement membrane. Leukocytes use integrins and proteases to adhere to and drill through blood vessel walls as they exit. Entrance into lymph vessels, however, is mysteriously different because it requires neither tool. To figure out how leukocytes barge in, Pflicke and Sixt used live cell imaging to follow DC migration in explanted skin from mouse ears.
A close look at the lymphatic basement membrane revealed periodic perforations. DCs squeezed through these holes by inserting projections and then swelling until the gaps widened enough for the cell bodies to slip through. At the next barrier, the lymphatic endothelium, the cells took advantage of flexible oak leaf–shaped junctions, which are known to flap open in only one direction, allowing the cells in but not out.
This manner of DC lymphatic travel may not apply outside of the afferent lymphatic system because not all linings bear pores or hinge-like junctions. Entering and exiting blood vessels, for example, might be more restricted because blood vessels must be tightly sealed against fluid leaks. Nonetheless, lymphatic migration is far from free-form. Visualizing the chemokine gradients that likely steer DCs into and around lymphatic vessels is the team's next challenge.