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Updated: Oct 15, 2025
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A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
Published on: June 8, 2022
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Blood-thirsty: S1PR5 and TRM
Victoria M Hallisey1, Susan R Schwab1
1Skirball Institute of Biomolecular Medicine, New York University Grossman School of Medicine, New York, NY.
The Journal of Experimental Medicine
|October 29, 2021
Summary
Sphingosine 1-phosphate receptor 5 (S1PR5) inhibits tissue-resident memory T cell (TRM) formation. Tissue-derived TGF-β restricts S1PR5 expression on infiltrating T cells, impacting TRM development.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Tissue-resident memory T cells (TRMs) are crucial for adaptive immunity.
- Understanding factors that regulate TRM formation is vital for vaccine development and immunotherapy.
- Sphingosine 1-phosphate receptors (S1PRs) are known regulators of lymphocyte trafficking and function.
Purpose of the Study:
- To investigate the role of sphingosine 1-phosphate receptor 5 (S1PR5) in the formation of tissue-resident memory T cells (TRMs).
- To identify mechanisms by which S1PR5 expression is regulated in T cells infiltrating tissues.
Main Methods:
- Flow cytometry analysis of T cell populations.
- Gene expression analysis of S1PR5 in T cells.
- In vivo models to study T cell homing and retention.
- In vitro stimulation assays with TGF-β.
Main Results:
- S1PR5 expression was found to significantly impair the formation of functional TRMs.
- Tissue-derived transforming growth factor-beta (TGF-β) was identified as a key regulator limiting S1pr5 expression on infiltrating T cells.
- Reduced S1PR5 expression correlated with enhanced TRM development.
Conclusions:
- S1PR5 acts as a potent inhibitor of tissue-resident memory T cell generation.
- TGF-β in the tissue microenvironment plays a critical role in modulating S1PR5 expression and thereby promoting TRM formation.
- Targeting the S1PR5 pathway or leveraging TGF-β signaling could offer novel strategies for enhancing T cell-mediated immunity.
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