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Egress: a receptor-regulated step in lymphocyte trafficking
Hugh Rosen1, Germana Sanna, Christopher Alfonso
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA. hrosen@scripps.edu
Immunological Reviews
|September 13, 2003
Summary
Sphingosine-1-phosphate (S1P) receptor agonism rapidly inhibits lymphocyte egress, causing lymphopenia and suppressing immune responses. This mechanism offers potential therapeutic benefits for transplantation and autoimmune diseases.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Lymphocyte recirculation through secondary lymphoid organs is crucial for immune responses.
- Lymphocyte egress is regulated by sphingosine-1-phosphate (S1P) receptors.
- S1P receptor agonism inhibits T and B cell egress from lymphoid organs.
Purpose of the Study:
- To investigate the role of S1P receptor signaling in lymphocyte trafficking.
- To explore the impact of S1P receptor agonism on immune responses.
- To evaluate the therapeutic potential of modulating S1P receptor activity.
Main Methods:
- Administration of S1P receptor agonists.
- Monitoring lymphocyte numbers in peripheral blood and lymphoid organs.
- Assessing immune responses to antigen challenge.
- Evaluating outcomes in models of transplantation and autoimmune disease.
Main Results:
- S1P receptor agonism caused rapid and sustained peripheral blood lymphopenia.
- Effector T cells were sequestered in lymph nodes, failing to reach circulation.
- Antigenic responses to peripheral antigens were suppressed.
- Significant immunosuppression was observed in transplantation and autoimmune models.
Conclusions:
- The S1P receptor system regulates lymphocyte traffic and immune responses.
- Pharmacological targeting of S1P receptors can induce immunosuppression.
- Inhibition of lymphocyte egress via S1P receptor agonism shows potential for treating autoimmune diseases and in transplantation.