Sphingosine-1-Phosphate Receptor 1 Is Involved in Non-Obese Diabetic Mouse Thymocyte Migration Disorders

International Journal of Molecular Sciences
Julia P LemosDaniella Areas Mendes-da-Cruz

Abstract

NOD (non-obese diabetic) mice spontaneously develop type 1 diabetes following T cell-dependent destruction of pancreatic β cells. Several alterations are observed in the NOD thymus, including the presence of giant perivascular spaces (PVS) filled with single-positive (SP) CD4⁺ and CD8⁺ T cells that accumulate in the organ. These cells have a decreased expression of membrane CD49e (the α5 integrin chain of the fibronectin receptor VLA-5 (very late antigen-5). Herein, we observed lower sphingosine-1-phosphate receptor 1 (S1P1) expression in NOD mouse thymocytes when compared with controls, mainly in the mature SP CD4⁺CD62Lhi and CD8⁺CD62Lhi subpopulations bearing the CD49e− phenotype. In contrast, differences in S1P1 expression were not observed in mature CD49e⁺ thymocytes. Functionally, NOD CD49e− thymocytes had reduced S1P-driven migratory response, whereas CD49e⁺ cells were more responsive to S1P. We further noticed a decreased expression of the sphingosine-1-phosphate lyase (SGPL1) in NOD SP thymocytes, which can lead to a higher sphingosine-1-phosphate (S1P) expression around PVS and S1P1 internalization. In summary, our results indicate that the modulation of S1P1 expression and S1P/S1P1 interactions ...Continue Reading

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Citations

Dec 22, 2019·International Journal of Molecular Sciences·Cecília R PantaZoltán Benyó
Aug 21, 2020·BMC Veterinary Research·Mayara BringelWalter Luiz Siqueira
May 1, 2020·International Journal of Molecular Sciences·Michele Dei CasFrancesco Secundo
Aug 8, 2020·Cells·Ewa Gurgul-Convey
Jun 8, 2021·Frontiers in Endocrinology·Christina Christoffersen

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Methods Mentioned

BETA
flow cytometry
GTPases
ubiquitination
FACS

Software Mentioned

Axio Vision Rel
Expression Suite
ImageJ ImageJ
GraphPad
GraphPad Prism

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