Role of sphingophospholipid receptors in the immune system

The group of Sphingosine-1-phosphate (S1P) receptors comprises five G protein-coupled receptors mediating a wide variety of biological functions. In order to characterize the as yet unidentified in vivo function of the S1P4 receptor that was initially described in our laboratory, we have created and analysed a S1P4-/-mouse model. The phenotype of these knock-out animals suggest a role of S1P4 in megakaryocyte maturation as well as in T cell biology. The biological behaviour of S1P4-deficient lymphocytes suggests furthermore an intricate interaction of the two S1P receptors predominantly expressed on lymphocytes, S1P1 and S1P4. In order to further dissect these mechanisms, we have generated lentiviral vectors for stable gene knock-down of S1P1 gene expression in hematopoietic cells. S1P4-deficient mice and the lentiviral siRNA vector system will be used conjointly to further delineated the role of S1P4 in the immune homeostasis.