Abnormal Lymphatic Sphingosine-1-Phosphate Signaling Aggravates Lymphatic Dysfunction and Tissue Inflammation
Authors' conclusion
This study suggests that reduction of the LEC S1P signaling aggravates lymphedema by enhancing LEC adhesion and amplifying pathogenic CD4 T-cell responses.
Study context
- Population
- Human and mouse lymphedema (mouse model: surgical ligation of tail lymphatics; Lymphatic endothelial cell (LEC)-specific S1pr1-deficient mice)
Main finding
As reported in the abstract
- Human and experimental lymphedema tissues showed decreased LEC S1P signaling through S1PR1
- LEC S1pr1 loss-of-function exacerbated lymphatic vascular insufficiency, tail swelling and CD4 T-cell infiltration in mouse lymphedema
- LECs from S1pr1LECKO mice cocultured with CD4 T cells augmented lymphocyte differentiation
- Inhibiting S1PR1 signaling in human dermal LECs promoted Th1 and Th2 differentiation through direct cell contact
- Human dermal LECs with dampened S1P signaling showed enhanced P-selectin
- In vitro P-selectin blockade reduced activation and differentiation of Th cells cocultured with shS1PR1-treated human dermal LECs
- P-selectin-directed antibody improved tail swelling and reduced Th1/Th2 responses in mouse lymphedema
Original publication
Abnormal Lymphatic Sphingosine-1-Phosphate Signaling Aggravates Lymphatic Dysfunction and Tissue Inflammation. Circulation. Published 23 August 2023. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →