Imaging leukocyte migration through afferent lymphatics*

Abstract

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]

CCR7-guided neutrophil redirection to skin-draining lymph nodes regulates cutaneous inflammation and infection

“…When recruited to a site of infection, antigen-specific effector T cells down-regulate CCR7 and remain in the tissue to carry out their effector functions ( 51 ). Conversely, effector T cells not specific for the pathogen maintain high surface levels of CCR7 ( 52 , 53 ). This mechanism retains antigen-specific T cells in the affected tissue, whereas it allows nonspecific T cells to migrate via CCL21 + lymphatics to dLNs where clearance of these cells prevents inflammatory damage.…”

Laponite Lights Calcium Flickers by Reprogramming Lysosomes to Steer DC Migration for An Effective Antiviral CD8+ T‐Cell Response

“…DC migration is tightly regulated by a large variety of signals, among which the receptor–chemokine axes and cytoskeleton play important roles. [ 26 ] The chemokine receptors CCR5, CCR7, and CXCR4 on DCs, which are important for tissue‐resident DCs to overcome extracellular matrix barriers and enter lymph vessels, were detected by fluorescence‐activated cell sorting (Figure 2d ). [ 27 ] CCR5, CCR7, and CXCR4 were strikingly upregulated after Lap treatment, with respective increases of 4.6, 3.6, and 6.9‐fold compared with PBS‐DCs, suggesting that Lap can enhance DC chemotaxis for multiple chemokines, including MIP/RANTES (CCR5 ligand), CCL19/21 (CCR7 ligand), and CXCL12 (CXCR4 ligand).…”

Pannexin1 deletion in lymphatic endothelium affects lymphatic function in a sex‐dependent manner

“…Finally, DC migration to draining LNs was only enhanced in female mice upon Panx1 deletion from LECs (Figure 6b ). DCs closely interact with LECs within capillaries and detach from these cells once they arrive in the collecting lymphatics, where lymph flow is enhanced (Collado‐Diaz et al., 2022 ). DCs are guided from the interstitium towards the lymphatic capillaries by CCL21 gradients, which are secreted by the LECs upon a Ca 2+ influx stimulated by LEC‐DC contacts (Vaahtomeri et al., 2017 ).…”

“…Draining LNs receive immune cells, such as dendritic cells (DCs), from inflamed tissues. Chemokine gradients regulate the entrance of DCs into and their exit from lymphatic vessels, and DCs actively interact with LECs during their journey (Collado‐Diaz et al., 2022 ). Subsequently, the lymph drains into the thoracic duct or right lymphatic trunk to return to the bloodstream (Aspelund et al., 2016 ).…”