TY - JOUR
T1 - Sphingosine 1-phosphate receptor modulators
T2 - A new class of immunosuppressants
AU - Yopp, Adam C.
AU - Ledgerwood, Levi G.
AU - Ochando, Jordi C.
AU - Bromberg, Jonathan S.
PY - 2006/11
Y1 - 2006/11
N2 - In this review, we summarize how FTY720 came from the lab bench to the bedside by examining its structural similarities to natural occuring sphingosine analogues, the mechanism of action, and clinical applicability to not only transplantation but also autoimmune, oncological, and neurobiological fields. FTY720, a sphingosine 1-phosphate (S1P) analogue, promotes the survival of human and animal allografts by sequestering T lymphocytes within peripheral lymphoid tissue. The mechanism of sequestration is three-fold:(1) T lymphocytes are driven into peripheral lymph nodes in a chemokine dependent manner by FTY720;(2) FTY720 downregulates sphingosine 1-phosphate receptors (S1PRs) on the T lymphocyte surface, rendering it unable to migrate along a S1P gradient; and (3) FTY720 closes stromal gates on the abluminal side of the lymphatic endothelium. Future areas of investigation include developing S1P analogues that have specific agonist binding to S1PRs avoiding side effects seen in non-specific binding.
AB - In this review, we summarize how FTY720 came from the lab bench to the bedside by examining its structural similarities to natural occuring sphingosine analogues, the mechanism of action, and clinical applicability to not only transplantation but also autoimmune, oncological, and neurobiological fields. FTY720, a sphingosine 1-phosphate (S1P) analogue, promotes the survival of human and animal allografts by sequestering T lymphocytes within peripheral lymphoid tissue. The mechanism of sequestration is three-fold:(1) T lymphocytes are driven into peripheral lymph nodes in a chemokine dependent manner by FTY720;(2) FTY720 downregulates sphingosine 1-phosphate receptors (S1PRs) on the T lymphocyte surface, rendering it unable to migrate along a S1P gradient; and (3) FTY720 closes stromal gates on the abluminal side of the lymphatic endothelium. Future areas of investigation include developing S1P analogues that have specific agonist binding to S1PRs avoiding side effects seen in non-specific binding.
KW - FTY720
KW - Immunosuppression transplantation
KW - T lymphocyteo
UR - http://www.scopus.com/inward/record.url?scp=33750796488&partnerID=8YFLogxK
U2 - 10.1111/j.1399-0012.2006.00570.x
DO - 10.1111/j.1399-0012.2006.00570.x
M3 - Review article
C2 - 17100731
AN - SCOPUS:33750796488
SN - 0902-0063
VL - 20
SP - 788
EP - 795
JO - Clinical Transplantation
JF - Clinical Transplantation
IS - 6
ER -