Fig. 1

Multistep homing process of lymphocytes. The top panel depicts the multistep adhesion cascade involved in lymphocyte homing: step 1: tethering and rolling. Tethering is mediated primarily by selectins, which can engage with their ligands rapidly with high tensile strength, enabling the capture of leukocytes out of the bloodstream. Integrins facilitate leukocytes’ slower rolling along endothelial cells following capture [37,38,39]. The adhesive interactions in this step are notably reversible and transient. Step 2: integrin activation. External stimuli are required for integrin affinity modulation [40]. Integrins have three conformational states with differing affinities [40]: (i) bent head-piece conformation with low affinity, (ii) extended head-piece conformation with intermediate affinity, and (iii) extended head-piece conformation with high affinity. Specific endothelial chemokines can rapidly (within milliseconds) enhance integrin affinity [41]. Step 3: arrest. This step is mediated by activated integrins, whereby lymphocytes adhere firmly to the endothelium and come to a complete stop. The bottom of the diagram shows the predominant molecules expressed on lymphocytes and endothelial cells involved at each step [27, 29, 42].. The arrows between them represent potential interactions (broken arrows indicate weak binding)