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Science 13 April 2007:
Vol. 316. no. 5822, p. 169
DOI: 10.1126/science.316.5822.169j
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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. (p. 295, published online 15 March; see the Perspective by Chun) 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.




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Science. ISSN 0036-8075 (print), 1095-9203 (online)