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Updated: Aug 7, 2026
Rapid and Robust Analysis of Cellular and Molecular Polarization Induced by Chemokine Signaling
Published on: December 12, 2014
Cutting edge: suppression of T cell chemotaxis by sphingosine 1-phosphate
Markus Graeler1, Geetha Shankar, Edward J Goetzl
1Department of Medicine, University of California Medical Center, 533 Parnassus at 4th, San Francisco, CA 94143, USA.
Abstract:
Murine CD4 and CD8 T cells express predominantly types 1 and 4 sphingosine 1-phosphate (S1P) G protein-coupled receptors (designated S1P1 and S1P4 or previously endothelial differentiation gene-encoded 1 and 6) for S1P, which has a normal plasma concentration of 0.1-1 microM. S1P now is shown to enhance chemotaxis of CD4 T cells to CCL-21 and CCL-5 by up to 2.5-fold at 10 nM to 0.1 microM, whereas 0.3-3 microM S1P inhibits this chemotaxis by up to 70%. Chemotaxis of S1P(1), but not S1P(4), transfectants to CXCL1 and CXCL4 was similarly affected by S1P. Activation of CD4 T cells, which decreases S1P receptor expression, suppressed effects of S1P on chemotaxis. Pretreatment of labeled CD4 T cells with S1P before reintroduction into mice inhibited by a maximum of 75% their migration into chemokine-challenged s.c. air pouches. The S1P-S1P(1) receptor axis thus controls recruitment of naive T cells by maintaining their response threshold to diverse lymphotactic factors.
Insights
Sphingosine 1-phosphate (S1P) regulates T cell migration. The S1P-S1P1 receptor pathway controls naive T cell recruitment by adjusting their response to lymphotactic factors.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Murine CD4 and CD8 T cells express sphingosine 1-phosphate (S1P) receptors S1P1 and S1P4.
- Plasma S1P concentration typically ranges from 0.1-1 microM.
Purpose of the Study:
- To investigate the role of S1P and its receptors in T cell chemotaxis.
- To elucidate the S1P-S1P1 receptor axis in naive T cell recruitment.
Main Methods:
- Studied chemotaxis of murine CD4 T cells in response to S1P and chemokines (CCL-21, CCL-5, CXCL1, CXCL4).
- Utilized S1P1 and S1P4 transfectants to assess receptor-specific effects.
- Examined the impact of T cell activation on S1P receptor expression and S1P effects.
- Assessed T cell migration in vivo using a murine air pouch model.
Main Results:
- S1P enhanced CD4 T cell chemotaxis at nanomolar to low micromolar concentrations (10 nM to 0.1 microM).
- Higher S1P concentrations (0.3-3 microM) inhibited chemotaxis.
- S1P affected chemotaxis via the S1P1 receptor, but not S1P4.
- T cell activation reduced S1P receptor expression and diminished S1P's effects.
- In vivo, S1P pretreatment inhibited T cell migration into chemokine-challenged air pouches by up to 75%.
Conclusions:
- The S1P-S1P1 receptor axis is crucial for controlling naive T cell recruitment.
- This axis modulates T cell responsiveness to various lymphotactic factors.
- S1P signaling plays a significant role in regulating T cell trafficking.
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