Tug of war at the exit door

Abstract

The lipid sphingosine-1-phosphate has been identified as a key exit signal for lymph nodes. In this issue of Immunity, Pham et al. (2008) show that its action can only be understood in the context of retention signals transduced by CCR7.

Figure 1

Three compartment model for a lymph node in which overplapping gradients of three chemokines CCL19/21 (green), CXCL13 (red) and CXCL12 (blue) define three parenchymal compartments, the deep paracortex, B cell follicles and medullary cords, respectively. These chemokines are captured on stromal cell surfaces, but are also may be detectable as gradients, particularly in boundary regions like those around the cortical sinusoid exit sites. The cortical and medullary sinusoids are bounded by lymphatic endothelial cells, which may have different properties. Pham et al provide evidence for functional S1P gradients that engage in a tug of war with CCL19/21 gradients around cortical sinusoids (purple), which are always permissive for T cell exit, whereas Wei et al (2005) provided evidence for control of exit at medullary sinisoids, in which S1P1 signaling closed exit doors.