Secrets and lyase: Control of sphingosine 1‐phosphate distribution

The signaling lipid sphingosine 1-phosphate (S1P) plays key roles in many physiological processes. In the immune system, S1P's best-described function is to draw cells out of tissues into circulation. Here, we will review models of S1P distribution in the thymus, lymph nodes, spleen, and nonlymphoid tissues. These models have been challenging to construct, because of the lack of tools to map lipid gradients. Nonetheless, evidence to date suggests that S1P distribution is exquisitely tightly controlled, and that concentrations of signaling-available S1P cannot be predicted by standard rules of thumb. The fine regulation of S1P gradients may explain how S1P can simultaneously direct multiple cell movements both between tissues and circulation and within tissues. It may also make it feasible to develop drugs that enable spatially specific modulation of S1P signaling.