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SPHINGOSINE-1-PHOSPHATE RECEPTOR 1 IS INVOLVED IN NON-OBESE DIABETIC MOUSE THYMOCYTE MIGRATION DISORDERS
camundongos diabéticos não obesos
migração celular
esfingosina-1-fosfato
receptor de esfingosina-1-fosfato 1
thymus
sphingosine-1-phosphate
sphingosine-1-phosphate receptor 1
VLA-5 (very late antigen-5)
cell migration
Autor
Afiliación
Resumen en ingles
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 in NOD mouse thymocytes are part of the T-cell migratory disorder observed during the pathogenesis of type 1 diabetes.
Palabras clave en portugues
Timocamundongos diabéticos não obesos
migração celular
esfingosina-1-fosfato
receptor de esfingosina-1-fosfato 1
Palabras clave en ingles
non-obese diabetic micethymus
sphingosine-1-phosphate
sphingosine-1-phosphate receptor 1
VLA-5 (very late antigen-5)
cell migration
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