Dendritic cell (DC) migration to draining lymph nodes (dLNs) is a slow process that is believed to begin with DCs approaching and entering into afferent lymphatic capillaries. From capillaries, DCs slowly crawl into lymphatic collectors, where lymph flow induced by collector contraction supports DC detachment and thereafter rapid, passive transport to dLNs. Performing a transcriptomics analysis of dermal endothelial cells, we found that inflammation induces the degradation of the basement membrane (BM) surrounding lymphatic collectors and preferential up-regulation of the DC trafficking molecule VCAM-1 in collectors. In crawl-in experiments performed in ear skin explants, DCs entered collectors in a CCR7- and β1 integrin–dependent manner. In vivo, loss of β1-integrins in DCs or of VCAM-1 in lymphatic collectors had the greatest impact on DC migration to dLNs at early time points when migration kinetics favor the accumulation of rapidly migrating collector DCs rather than slower capillary DCs. Taken together, our findings identify collector entry as a critical mechanism enabling rapid DC migration to dLNs in inflammation.

Highlights d ACKR4 is expressed in a flow-dependent manner in afferent lymphatic collectors d ACKR4 scavenges CCR7 ligands like CCL21 and removes them from the collector surface d Chemokine scavenging prevents T cell accumulation in inflamed dermal collectors d In the absence of ACKR4, T cell migration to draining lymph nodes is reduced

To fulfill their function of immune defense and surveillance, most leukocytes are not stationary positioned in the body but constantly migrate within tissues or circulate between tissues and organs. 1,2 Considering that active interstital migration is very slow, leukocytes use blood and lymphatic vessels to rapidly move between different sites of the body. Over the past decades, the process of immune cell migration out of blood vessels has been studied in great detail, culminating in the identification of the intravascular adhesion cascade and a plethora of molecules involved in leukocyte extravasation from different blood vascular beds in steady-state and in inflammation. [3][4][5]