Figure 3.

Leukocyte migration through afferent lymphatics occurs in a step-wise manner. (A) Summary of the key steps in DC and T cell migration from peripheral tissues through afferent LVs. (B) Description of the individual steps. Step 1: Interstitial migration: The interstitial space is comprised of fibroblasts and extracellular matrix (ECM) through which DC and T cells migrate in an ameboid fashion towards initial lymphatic capillaries. Step 2: Capillary entry: Attracted by the peri-lymphatic CCL21 chemokine gradient, DCs and T cells approach blind-ended capillaries and enter through specialized flaps formed by discontinuously joint capillary LECs (capLECs). Step 3: Intralymphatic crawling: DCs and T cells actively crawl and patrol within the capillary lumen, thereby interacting with the lymphatic endothelium. Step 4: Passive transport: migratory DCs and T cells eventually reach the downstream collecting vessels segments. Here, lymph flow increases due to vessel contractions mediated by the collector-surrounding lymphatic muscle cells (LMCs), leading to the detachment of leukocytes and their passive and rapid transport towards the dLN. X: Shortcut into afferent LVs: Under inflammatory conditions, DCs can additionally transmigrate and directly enter into lymphatic collectors [74].