Sphingosine 1-phosphate (S1P) is a circulating lipid mediator that induces the egress of lymphocytes from lymphoid organs. The immunomodulatory effects of S1P are made apparent by the absence of circulating lymphocytes in mice that are unable to support its production and by the encouraging results of clinical trials aimed at targeting this pathway to suppress transplant rejection and autoimmunity. Pappu et al. use a combination of conditional gene deletion and bone marrow chimerism to illuminate two sources of S1P in the blood and lymphatic circulation. By sustaining S1P levels outside the lymphoid organs, these supplies allow lymphocytes to follow a gradient between the lymphoid tissue--where S1P is catabolized to low levels--and the two circulatory systems. This insight may help refine approaches of immune suppression and activation via the S1P pathway.
R. Pappu, S. R. Schwab, I. Cornelissen, J. P. Pereira, J. B. Regard, Y. Xu, E. Camerer, Y.-W. Zheng, Y. Huang, J. G. Cyster, S. R. Coughlin, Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science 316, 295-298 (2007). [Abstract] [Full Text]