Chemoattract receptor signaling and its role in lymphocyte motility and trafficking

Intravital microscopy has provided extraordinary glimpses of lymphocytes crossing high endothelial venules, detailed the movements and interactions of lymphocytes within lymph organs, and recorded lymphocytes crossing the lymphatic endothelium into the efferent lymph. Helping to orchestrate these movements are signals generated by the engagement of chemoattractants with their cognate receptors. Chemokines present on high endothelial venules and within lymph organs, and the high levels of sphingosine l-phosphate in the lymph, provide signposts to help guide lymphocytes and provide intracellular signals that affect lymphocyte polarity and motility. Within lymph nodes, T and B lymphocytes migrate along networks of fibroblastic reticular cells and follicular dendritic, respectively, which provide an adhesive platform and solid phased chemokines. Illustrating the importance of chemoattractant receptors in these processes, lymphocytes that lack CXCR4, CXCR5, CCR7 or S1PR1, or which lack crucial signaling molecules activated by these receptors, exhibit defects in lymph node entrance, positioning, polarity, motility, and/or lymph node egress. This review will focus on the contributions of in vivo imaging of lymphocytes from various mouse mutants to our understanding of the roles chemoattractants play in lymphocyte entrance into and exit from lymph nodes, and in coordinating and facilitating the movements of lymphocytes within lymph nodes.